Active and passive immunization against oral Candida albicans infection in a murine model

Background/aims: Clinical and laboratory studies are consistent with a major role for cell-mediated immunity in recovery from oral infection with Candida albicans, but the role of humoral immunity remains controversial. The purpose of this study was to establish the relative contributions of cellular and humoral immunity to protection against oral candidiasis in a murine model, and to determine whether host responses could be enhanced by different immunization strategies. Results: Active oral immunization was protective in BALB/c and CBA/CaH mice, reducing both fungal burden and duration of infection after secondary challenge, whereas systemic immunization failed to protect against subsequent oral challenge. Candida-specific IgM was the predominant antibody detected in serum following both primary and secondary oral challenge; however, Candida-specific salivary IgA was not detectable. Immunization by passive transfer of either lymphocytes or immune serum did not confer any significant protection against oral infection in either susceptible or resistant mouse strain. Conclusion: The data demonstrate a possible role for mucosa-associated immunity following active immunization by the oral route, most likely exerted by local T lymphocytes resident in the oral mucosa, but there was no evidence to support a role for humoral immunity in protection against oral candidiasis.

The effect of active immunization against adrenocorticotropic hormone on cortisol, beta-endorphin, vocalization, and growth in pigs

Because the poor growth performance of intensively housed pigs is associated with increased circulating glucocorticoid concentrations, we investigated the effects of glucocorticoid suppression by inducing a humoral immune response to ACTH on physiological and production variables in growing pigs. Grower pigs (28.6 0.9 kg) were immunized with amino acids 1 through 24 of ACTH conjugated to ovalbumin and suspended in diethylaminoethyl (DEAE) dextran-adjuvant or adjuvant alone (control) on d 1, 28, and 56. The ACTH-specific antibody titers generated suppressed increases in cortisol concentrations on d 63 in response to an acute stressor (P = 0.002; control = 71 +/- 8.2 ng/ mL; ACTH-immune = 43 +/- 4.9 ng/mL) without altering basal concentrations. Plasma beta-endorphin concentrations were also increased (P < 0.001) on d 63 (control = 18 +/- 2.1 ng/mL; ACTH-immune = 63 +/- 7.3 ng/mL), presumably because of a release from negative feedback on the expression of proopiomelanocortin in pituitary corticotropes. Immunization against ACTH did not alter ADG (P = 0.120; control = 1,077 25; ACTH-immune = 1,143 25 g) or ADFI (P = 0.64; control = 2,719 42; ACTH-immune = 2,749 42 g) and did not modify behavior (P = 0.681) assessed by measuring vocalization in response to acute restraint. In summary, suppression of stress-induced cortisol responses through ACTH immunization increased beta-endorphin concentrations, but it did not modify ADG, ADFI, or restraint vocalization score in growing pigs.

Method for the synthesis of highly pure vaccines using the lipid core peptide system

Traditional vaccines consisting of whole attenuated microorganisms, killed microorganisms, or microbial components, administered with an adjuvant (e.g. alum), have been proved to be extremely successful. However, to develop new vaccines, or to improve upon current vaccines, new vaccine development techniques are required. Peptide vaccines offer the capacity to administer only the minimal microbial components necessary to elicit appropriate immune responses, minimizing the risk of vaccination associated adverse effects, and focusing the immune response toward important antigens. Peptide vaccines, however, are generally poorly immunogenic, necessitating administration with powerful, and potentially toxic adjuvants. The attachment of lipids to peptide antigens has been demonstrated as a potentially safe method for adjuvanting peptide epitopes. The lipid core peptide (LCP) system, which incorporates a lipidic adjuvant, carrier, and peptide epitopes into a single molecular entity, has been demonstrated to boost immunogenicity of attached peptide epitopes without the need for additional adjuvants. The synthesis of LCP systems normally yields a product that cannot be purified to homogeneity. The current study describes the development of methods for the synthesis of highly pure LCP analogs using native chemical ligation. Because of the highly lipophilic nature of the LCP lipid adjuvant, difficulties (e.g. poor solubility) were experienced with the ligation reactions. The addition of organic solvents to the ligation buffer solubilized lipidic species, but did not result in successful ligation reactions. In comparison, the addition of approximately 1% (w/v) sodium dodecyl sulfate (SDS) proved successful, enabling the synthesis of two highly pure, tri-epitopic Streptococcus pyogenes LCP analogs. Subcutaneous immunization of B10.BR (H-2(k)) mice with one of these vaccines, without the addition of any adjuvant, elicited high levels of systemic IgG antibodies against each of the incorporated peptides. Copyright (c) 2006 European Peptide Society and John Wiley & Sons, Ltd.

Measurement of strain and strain rate by echocardiography - Ready for prime time?

Strain and strain rate (SR) are measures of deformation that are basic descriptors of both the nature and the function of cardiac tissue. These properties may now be measured using either Doppler or two-dimensional ultrasound techniques. Although these measurements are feasible in routine clinical echocardiography, their acquisition and analysis nonetheless presents a number of technical challenges and complexities. Echocardiographic strain and SR imaging has been applied to the assessment of resting ventricular function, the assessment of myocardial viability using low-dose dobutamine infusion, and stress testing for ischemia. Resting function assessment has been applied in both the left and the fight ventricles, and may prove particularly valuable for identifying myocardial diseases and following up the treatment response. Although the evidence base is limited, SR imaging seems to be feasible and effective for the assessment of myocardial viability. The use of the technique for the detection of ischemia during stress echocardiography is technically challenging and likely to evolve further. The clinical availability of strain and SR measurement may offer a solution to the ongoing need for quantification of regional and global cardiac function. Nonetheless, these techniques are susceptible to artifact, and further technical development is necessary.

Multiphoton high-resolution 3D imaging of Langerhans cells and keratinocytes in the mouse skin model adopted for epidermal powdered immunization

Langerhans cells (LCs) can be targeted with DNA-coated gold micro-projectiles ("Gene Gun") to induce potent cellular and humoral immune responses. It is likely that the relative volumetric distribution of LCs and keratinocytes within the epidermis impacts on the efficacy of Gene Gun immunization protocols. This study quantified the three-dimensional (3D) distribution of LCs and keratinocytes in the mouse skin model with a near-infrared multiphoton laser-scanning microscope (NIR-MPLSM). Stratum corneum (SC) and viable epidermal thickness measured with MPLSM was found in close agreement with conventional histology. LCs were located in the vertical plane at a mean depth of 14.9 mum, less than 3 mum above the dermo-epidermal boundary and with a normal histogram distribution. This likely corresponds to the fact that LCs reside in the suprabasal layer (stratum germinativum). The nuclear volume of keratinocytes was found to be approximately 1.4 times larger than that of resident LCs (88.6 mum3). Importantly, the ratio of LCs to keratinocytes in mouse ear skin (1:15) is more than three times higher than that reported for human breast skin (1:53). Accordingly, cross-presentation may be more significant in clinical Gene Gun applications than in pre-clinical mouse studies. These interspecies differences should be considered in pre-clinical trials using mouse models.

Protocol, image, and discourse in political leadership competition:the case of Prime Minister Lionel Jospin, 1997-2002

This article examines the relationship between Prime Minister Jospin and President Chirac in the period 1997 to 2002. It is concerned in particular with symbolism, discourse and protocol, and how these have mediated the political competition between Chirac and Jospin. We develop a framework of analysis with several main strands. We consider the effects of the institutions of the Fifth Republic upon the political conduct of Prime Minister and President. We observe the perceived character traits of the individuals concerned, as well as the character traits expected of the offices of President and Prime Minister. We investigate the influence of the past upon the behaviour of Chirac and Jospin in the present, both in terms of notions of regime crisis which configured the institutions in the first place, and in relation to the image of previous holders of the offices (especially Charles de Gaulle and Franois Mitterrand).

'The prime minister said...': voices in translated political texts

A variety of texts are translated to fulfil functions for political communication across languages, cultures, and ideologies. For example, newspapers regularly provide quotes of statements by foreign politicians, without explicitly indicating that these politicians were actually speaking in their own languages. Politicians react to statements by other politicians as they were presented to them in translation. Political scientists and other experts often debate the potential political consequences of (the translation of) a statement. This chapter addresses the (in)visibility of translation in political communication and the link between textual profiles of translations and the socio-political contexts in which they are produced. The analyses are conducted from the perspective of Translation Studies. The focus is on institutionalised forms of political discourse, i.e. texts that originate in political or media institutions. The link between translation profiles and the social, institutional, ideological conditions of text production is illustrated with reference to authentic political texts (interviews, speeches by politicians, press conferences), mainly involving English, French and German as source and target languages.

Molecular investigations into vaginal immunization with HIV gp41 antigenic construct H4A in a quick release solid dosage form

A robust vaginal immune response is considered essential for an effective prophylactic vaccine that prevents transmission of HIV and other sexually acquired diseases. Considerable attention has recently focused on the potential of vaginally administered vaccines as a means to induce such local immunity. However, the potential for vaccination at this site remains in doubt as the vaginal mucosa is generally considered to have low immune inductive potential. In the current study, we explored for the first time the use of a quick release, freeze-dried, solid dosage system for practical vaginal administration of a protein antigen. These solid dosage forms overcome the common problem associated with leakage and poor retention of vaginally administered antigen solutions. Mice were immunized vaginally with H4A, an HIV gp41 envelope based recombinant protein, using quick release, freeze-dried solid rods, and the immune responses compared to a control group immunized via subcutaneous H4A injection. Vaginally immunized mice failed to elicit robust immune responses. Our detailed investigations, involving cytokine analysis, the stability of H4A in mouse cervicovaginal lavage, and elucidation of the state of H4A protein in the immediate-release dosage form, revealed that antigen instability in vaginal fluid, the state of the antigen in the dosage form, and the cytokine profile induced are all likely to have contributed to the observed lack of immunogenicity. These are important factors affecting vaginal immunization and provide a rational basis for explaining the typically poor and variable elicitation of immunity at this site, despite the presence of immune responsive cells within the vaginal mucosae. In future mucosal vaccine studies, a more explicit focus on antigen stability in the dosage form and the immune potential of available antigen-responsive cells is recommended.

Hand in hand:privatising five star hotels in Egypt through the stock market will enhance the latter's role as well as set an example of the benefits that could be gained from privatisation

This thesis examines the possibility of privatising public owned five star hotels in Egypt through its stock market in order to give a boost to the Egyptian privatisation programme and to help activate its stock market. To explore these aspects, two main technical exercises were executed. First the writer constructed, for the first time in Egypt, a daily price index for Cairo Stock Exchange and an index for the tourism sector, in order to analyze the efficiency of the capital market. This technical analysis showed that Cairo stock exchange is inefficient, stagnant and undergoes minimal fluctuations, especially when compared to other developed and emerging markets. Second, given the importance and complexity of the valuation of SOEs prior to their privatisation, a sample of three five star hotels that could be prime candidates for privatisation via the stock market in Egypt were selected and a detailed financial analysis for the three hotels was concluded. The result was a valuation range for the three hotels using various valuation methods. Nevertheless it was found out that the final value of hotels will be determined by the market itself. Depite the inefficiency of Cairo Stock Exchange, the thesis did not rule out privatisation through the stock market. On the contrary it cited several examples of developing countries that were able to successfully privatise some of their SOEs via their rudimentary capital markets. Finally, the thesis recommended that five star hotels could be pefect candidates for privatisation via the stock market in Egypt. This is because five star hotels are profitable, privately managed, non strategic and not highly capital intensive businesses. In addition, they do not suffer from overstaffing and the industry in which they operate i.e. tourism sector, has high growth prospects and is of an international nature. Therefore it is anticipated that privatisation of five star hotels can attract a lot of investors because of the relatively high returns. This in turn will help activate and popularize the capital market in Egypt. At the same time the benefits of privatisation would be more visible which will give more momentum to the privatisation programme and make it more politically acceptable.

Designing a methodology for an office communication and information system:for executives in the Malaysian public sector : the Prime Minister's office

Modern managers are under tremendous pressure in attempting to fulfil a profoundly complex managerial task, that of handling information resources. Information management, an intricate process requiring a high measure of human cognition and discernment, involves matching a manager's lack of information processing capacity against his information needs, with voluminous information at his disposal. The nature of the task will undoubtedly become more complex in the case of a large organisation. Management of large-scale organisations is therefore an exceedingly challenging prospect for any manager to be faced with. A system that supports executive information needs will help reduce managerial and informational mismatches. In the context of the Malaysian public sector, the task of overall management lies with the Prime Minister and the Cabinet. The Prime Minister's Office is presently supporting the Prime Minister's information and managerial needs, although not without various shortcomings. The rigid formalised structure predominant of the Malaysian public sector, so opposed to dynamic treatment of problematic issues as faced by that sector, further escalates the managerial and organisational problem of coping with a state of complexity. The principal features of the research are twofold: the development of a methodology for diagnosing the problem organisation' and the design of an office system. The methodological development is done in the context of the Malaysian public sector, and aims at understanding the complexity of its communication and control situation. The outcome is a viable model of the public sector. `Design', on the other hand, is developing a syntax or language for office systems which provides an alternative to current views on office systems. The design is done with reference to, rather than for, the Prime Minister's Office. The desirable outcome will be an office model called Office Communication and Information System (OCIS).