Is vaccine therapy the future in cancer prevention?

One vaccine designed to prevent cancer by preventing a precursor infection is already in common use, and at least one more is in the latter stages of clinical development. These vaccines are part of a new era of cancer immunoprophylaxis. Several further vaccines are in preclinical and clinical development, targeted at preventing cancer precursor infections, and these should add to our ability to prevent this common human disorder. However, vaccines to prevent cancers not triggered by infection are a more remote prospect, for a variety of reasons.

A voice unknown: Undercurrents in Mussorgsky's 'Sunless'

Mussorgsky's Sunless cycle is aesthetically and stylistically an anomalous member of his oeuvre. Its notably effaced, pared-down, and withdrawn qualities present challenges to critical interpretation. Its uniqueness, however, renders it a crucial work for furnishing the fullest possible picture of Mussorgsky as a creative artist. The author of its texts, Golenishchev-Kutuzov (whose relationship with Mussorgsky at the time of its writing possibly extended beyond the platonic) has been identified by recent scholarship as an essential eye-witness for those to whom Stasov's populist characterization of the composer does not ring entirely true. Golenishchev-Kutuzov believed that in Sunless Mussorgsky first revealed his authentic artistic self. According to Golenishchev-Kutuvoz, Mussorgsky regarded his signal achievement in Sunless to have been the eradication of all elements other than feeling. In other words, he had thrown off the stylistic shackles imposed by the aesthetics of realism and relied entirely on intuitive harmonic invention as the sole conveyor of a purely subjective, affective meaning in the cycle. This hypothesis forms the point of departure for an investigation of select numbers of the cycle. Analysis reveals that the affective aspect is riot the only significant element operative. Alongside remnants of the realist style, there is evidence, of varying degrees of subtlety, for a knowing use of symmetrical pitch organization. Mussorgsky not only adapted the usual referential attachments of symmetrically based chromaticism-typically found in Russian operas of the second half of the nineteenth century-he also, through extremely simple but effective means, synthesized the intuitive harmonic and rational symmetrical elements of the cycle's pitch organization so that the latter emerges seamlessly out of the former. This remarkable synthesis ensures the cycle's uniformity of tone while also allowing for a reading that extends beyond the generally affective to the symbolically more specific. This symbolic level of reading offers several interpretative possibilities, one of which may refer even to the relationship of the poet and the composer. Irrespective of such potentials for interpretation, the most significant achievement in the cycle remains the synthesis of the intuitive/affective and rational/symbolic elements of its organization. Songs 1, 2, 3, and 6 of the cycle are considered in detail.

Cross-reactivity of GroEL antibodies with human heat shock protein 60 and quantification of pathogens in atherosclerosis

Background/aims: Chronic infections such as those caused by Chlamydia pneumoniae and periodontopathic bacteria such as Porphyromonas gingivalis have been associated with atherosclerosis, possibly due to cross-reactivity of the immune response to bacterial GroEL with human heat shock protein (hHSP) 60. Methods: We examined the cross-reactivity of anti-GroEL and anti-P. gingivalis antibodies with hHSP60 in atherosclerosis patients and quantified a panel of six pathogens in atheromas. Results: After absorption of plasma samples with hHSP60, there were variable reductions in the levels of anti-GroEL and anti-P. gingivalis antibodies, suggesting that these antibodies cross-reacted with hHSP60. All of the artery specimens were positive for P. gingivalis. Fusobacterium nucleatum, Tannerella forsythia, C. pneumoniae, Helicobacter pylori, and Haemophilus influenzae were found in 84%, 48%, 28%, 4%, and 4% of arteries, respectively. The prevalence of the three periodontopathic microorganisms, P. gingivalis, F. nucleatum and T. forsythia, was significantly higher than that of the remaining three microorganisms. Conclusions: These results support the hypothesis that in some patients, cross-reactivity of the immune response to bacterial HSPs including those of periodontal pathogens, with arterial endothelial cells expressing hHSP60 may be a possible mechanism for the association between atherosclerosis and periodontal infection.

Feral goat eradications on islands

Introduced mammals are major drivers of extinction. Feral goats (Capra hircus) are particularly devastating to island ecosystems, causing direct and indirect impacts through overgrazing, which often results in ecosystem degradation and biodiversity loss. Removing goat populations from islands is a powerful conservation tool to prevent extinctions and restore ecosystems. Goats have been eradicated successfully from 120 islands worldwide. With newly developed technology and techniques, island size is perhaps no longer a limiting factor in the successful removal of introduced goat populations. Furthermore,. the use of global positioning systems, geographic information systems, aerial hunting by helicopter specialized bunting dogs, and Judas goats has dramatically increased efficiency and significantly reduced the duration of eradication campaigns. Intensive monitoring programs are also critical for successful eradications. Because of the presence of humans with domestic goat populations on large islands, future island conservation actions will require eradication programs that involve local island inhabitants in a collaborative approach with biologists, sociologists, and educators. Given the clear biodiversity benefits, introduced goat populations should be routinely removed from islands.

Increasing the efficacy of Judas goats by sterilisation and pregnancy termination

The use of Judas goats to locate remnant animals is a potentially powerful tool for enhancing goat-eradication efforts, which are especially important to island conservation. However, current Judas goat methodology falls short of its potential efficacy. Female Judas goats are often pregnant at the time of deployment or become impregnated in the field; pregnant females leave associated goats to give birth, causing downtime of Judas goat operations. Further, male Judas goats may inseminate remnant females. Sterilising Judas goats prior to deployment removes these inefficiencies. Here, we describe two methods (epididymectomy for males and tubal occlusion for females) that sterilise Judas goats while still maintaining sexual motivation and other behaviours associated with intact animals. These surgeries are straightforward, time efficient, and may be conducted in the field by staff with minimal training. Given the widespread and deleterious impacts of non-native herbivores to ecosystems and the importance of Judas operations in detecting animals at low densities, sterilisation and termination of pregnancy should be applied routinely in Judas goat (and possibly other species) programs to increase the efficacy of low-density control operations and eradication campaigns.

The effects of ionizing radiation on the reproductive capacity of adult Penaeus (Marsupenaeus) japonicus (Bate)

The reproductive capacity of adult Penaeus (Marsupenaeus) japonicus (Bate) was assessed after exposure to ionizing gamma radiation from a cobalt-60 source. Males and females were each exposed to 0, 10 and 20 Gray (Gy) of ionizing radiation (IR) and reciprocally crossed to give nine mating combinations. Fecundity and hatch rate of resulting spawnings were used as measures of reproductive capacity. IR significantly (P

Polioviruses and other enteroviruses isolated from faecal samples of patients with acute flaccid paralysis in Australia, 1996-2004

Background: Acute flaccid paralysis (AFP) is the most common clinical presentation of acute poliovirus infection, occurring in 0.1-1% of infected cases. AFP surveillance has been used world-wide to monitor the control and eradication of circulating wild poliovirus. This study aims to review the significance of all enteroviruses, including polioviruses, isolated from patients with AFP in Australia between 1996 and 2004. Methods: We undertook a retrospective review of all notified cases of AFP, aged 0-15 years and resident in Australia at the time of notification. We reviewed all available clinical and virological data for these cases and all records of the Polio Expert Committee, which determined the final classification for all cases. Results: There were 335 notified cases that satisfied the case definition for AFP, 162 (48%) of whom had at least one faecal sample tested. Enteroviruses isolated from the faeces of 26 (16%) of the 162 cases were Coxsackie A24, Coxsackie B5, enterovirus 71, enterovirus 75, echovirus 9, echovirus 11 and echovirus 18. In addition, one or more polioviruses were isolated from the faeces of seven patients. Six of seven polioviruses were characterised as Sabin-like, one was not characterised, but all were considered to be incidental isolates. Five of these cases were classified as infant botulism, one case as transverse myelitis and one as a focal mononeuropathy. Conclusion: With the eradication of circulating wild polioviruses, other enteroviruses are being more commonly identified as the cause of polio-like illnesses. In the polio end game, when there is increased testing for polioviruses, it is important to consider infant botulism as a differential diagnosis in cases presenting with AFP.

Detection and discrimination of herpes simplex viruses, Haemophilus ducreyi, Treponema pallidum, and Calymmatobacterium (Klebsiella) granulomatis from genital ulcers

Background. Genital ulcer disease (GUD) is commonly caused by pathogens for which suitable therapies exist, but clinical and laboratory diagnoses may be problematic. This collaborative project was undertaken to address the need for a rapid, economical, and sensitive approach to the detection and diagnosis of GUD using noninvasive techniques to sample genital ulcers. Methods. The genital ulcer disease multiplex polymerase chain reaction (GUMP) was developed as an inhouse nucleic acid amplification technique targeting serious causes of GUD, namely, herpes simplex viruses (HSVs), Haemophilus ducreyi, Treponema pallidum, and Klebsiella species. In addition, the GUMP assay included an endogenous internal control. Amplification products from GUMP were detected by enzyme linked amplicon hybridization assay (ELAHA). Results. GUMP-ELAHA was sensitive and specific in detecting a target microbe in 34.3% of specimens, including 1 detection of HSV-1, three detections of HSV-2, and 18 detections of T. pallidum. No H. ducreyi has been detected in Australia since 1998, and none was detected here. No Calymmatobacterium ( Klebsiella) granulomatis was detected in the study, but there were 3 detections during ongoing diagnostic use of GUMP-ELAHA in 2004 and 2005. The presence of C. granulomatis was confirmed by restriction enzyme digestion and nucleotide sequencing of the 16S rRNA gene for phylogenetic analysis. Conclusions. GUMP-ELAHA permitted comprehensive detection of common and rare causes of GUD and incorporated noninvasive sampling techniques. Data obtained by using GUMP-ELAHA will aid specific treatment of GUD and better define the prevalence of each microbe among at-risk populations with a view to the eradication of chancroid and donovanosis in Australia.

Management of plant invasions mediated by frugivore interactions

1. Some of the most damaging invasive plants are dispersed by frugivores and this is an area of emerging importance in weed management. It highlights the need for practical information on how frugivores affect weed population dynamics and spread, how frugivore populations are affected by weeds and what management recommendations are available. 2. Fruit traits influence frugivore choice. Fruit size, the presence of an inedible peel, defensive chemistry, crop size and phenology may all be useful traits for consideration in screening and eradication programmes. By considering the effect of these traits on the probability, quality and quantity of seed dispersal, it may be possible to rank invasive species by their desirability to frugivores. Fruit traits can also be manipulated with biocontrol agents. 3. Functional groups of frugivores can be assembled according to broad species groupings, and further refined according to size, gape size, pre- and post-ingestion processing techniques and movement patterns, to predict dispersal and establishment patterns for plant introductions. 4. Landscape fragmentation can increase frugivore dispersal of invasives, as many invasive plants and dispersers readily use disturbed matrix environments and fragment edges. Dispersal to particular landscape features, such as perches and edges, can be manipulated to function as seed sinks if control measures are concentrated in these areas. 5.Where invasive plants comprise part of the diet of native frugivores, there may be a conservation conflict between control of the invasive and maintaining populations of the native frugivore, especially where other threats such as habitat destruction have reduced populations of native fruit species. 6. Synthesis and applications. Development of functional groups of frugivore-dispersed invasive plants and dispersers will enable us to develop predictions for novel dispersal interactions at both population and community scales. Increasingly sophisticated mechanistic seed dispersal models combined with spatially explicit simulations show much promise for providing weed managers with the information they need to develop strategies for surveying, eradicating and managing plant invasions. Possible conservation conflicts mean that understanding the nature of the invasive plant-frugivore interaction is essential for determining appropriate management.

Allergy - 5: Allergy and the skin: eczema and chronic urticaria

Eczema is common, occurring in 15%-20% of infants and young children. For some infants it can be a severe chronic illness with a major impact on the child's general health and on the family. A minority of children will continue to have eczema as adults. The exact cause of eczema is not clear, but precipitating or aggravating factors may include food allergens (most commonly, egg) or environmental allergens/irritants, climatic conditions, stress. and genetic predisposition. Management of eczema consists of education; avoidance of triggers and allergens; liberal use of emollients or topical steroids to control inflammation; use of antihistamines to reduce itch; and treatment of infection if present. Treatment with systemic agents may be required in severe cases, but must be supervised by an immunologist. Urticaria (hives) may affect up to a quarter of people at some time in their lives. Acute urticaria is more common in children, while chronic urticaria is more common in adults. Chronic urticaria is not life-threatening, but the associated pruritus and unsightly weals can cause patients much distress and significantly affect their daily lives. Angioedema coexists with urticaria in about 50% of patients. It typically affects the lips, eyelids, palms, soles and genitalia. Management of urticaria is through education; avoidance of triggers and allergens (where relevant); use of antihistamines to reduce itch; and short-term use of corticosteroids when antihistamine therapy is ineffective. Referral is indicated for patients with resistant disease.

Host-bacteria interactions : Host cell responses and bacterial pathogenesis

Helicobacter pylori colonizes the human stomach, where it causes gastritis that may develop into peptic ulcer disease or cancer when left untreated. Neisseria gonorrhoeae colonizes the urogenital tract and causes the sexually transmitted disease gonorrhea. In contrast, Lactobacillus species are part of the human microbiota, which is the resident microbial community, and are considered to be beneficial for health. The first host cell types that bacteria encounter when they enter the body are epithelial cells, which form the border between the inside and the outside, and macrophages, which are immune cells that engulf unwanted material.       The focus of this thesis has been the interaction between the host and bacteria, aiming to increase our knowledge of the molecular mechanisms that underlie the host responses and their effects on bacterial pathogenicity. Understanding the interactions between bacteria and the host will hopefully enable the development of new strategies for the treatment of infectious disease. In paper I, we investigated the effect of N. gonorrhoeae on the growth factor amphiregulin in cervical epithelial cells and found that the processing and release of amphiregulin changes upon infection. In paper II, we examined the expression of the transcription factor early growth response-1 (EGR1) in epithelial cells during bacterial colonization. We demonstrated that EGR1 is rapidly upregulated by many different bacteria. This upregulation is independent of the pathogenicity, Gram-staining type and level of adherence of the bacteria, but generally requires viable bacteria and contact with the host cell. The induction of EGR1 is mediated primarily by signaling through EGFR, ERK1/2 and β1-integrins. In paper III, we described the interactions of the uncharacterized protein JHP0290, which is secreted by H. pylori, with host cells. JHP0290 is able to bind to several cell types and induces apoptosis and TNF release in macrophages. For both of these responses, signaling through Src family kinases and ERK is essential. Apoptosis is partially mediated by TNF release. Finally, in paper IV, we showed that certain Lactobacillus strains can reduce the colonization of H. pylori on gastric epithelial cells. Lactobacilli decrease the gene expression of SabA and thereby inhibit the binding mediated by this adhesin.

Active membrane transport and receptor proteins from bacteria

A general strategy for the expression of bacterial membrane transport and receptor genes in Escherichia coli is described. Expression is amplified so that the encoded proteins comprise 5-35% of E. coli inner membrane protein. Depending upon their topology, proteins are produced with RGSH6 or a Strep tag at the C-terminus. These enable purification in mg quantities for crystallization and NMR studies. Examples of one nutrient uptake and one multidrug extrusion protein from Helicobacter pylori are described. This strategy is successful for membrane proteins from H. pylori, E. coli, Enterococcus faecalis, Bacillus subtilis, Staphylococcus aureus, Microbacterium liquefaciens, Brucella abortus, Brucella melitensis, Campylobacter jejuni, Neisseria meningitides, Streptomyces coelicolor and Rhodobacter sphaeroides. ©2005 Biochemical Society.

Género y traducción:elementos discursivos para una reescritura feminista

Este artículo explora el binomio género y traducción desde la convicción de que ésta última, al constituir un punto de contacto entre realidades lingüísticas, culturales e ideológicas diferentes, desempeña un decisivo papel en el cambio de la naturaleza patriarcal y sexista del lenguaje y de las sociedades. Para comenzar a abordarlo, reflexionaré sobre las influencias y confluencias entre traducción y feminismos, que tanto han contribuido a la renovación y enriquecimiento mutuo de ambas disciplinas. Esta perspectiva me ubicará en una posición privilegiada desde la que plantear el compromiso de la traducción feminista, materializado en la adaptación (más que invención) de estrategias ideológicas y textuales legítimas para traducción, con las que contribuir a la implementación de la reforma lingüística y social superadora de la discriminación de género. This article explores the relationship between gender and translation with the conviction that the latter is a point of contact between different linguistic, cultural and ideological realities, and therefore plays a vital role in the change of the patriarchal and sexist nature of language and societies. I will begin by examining the influences and confluences between translation and feminisms, which have powerfully contributed to the mutual renewal and enrichment of both disciplines. This perspective will place me in a privileged position from which I will consider the purpose of feminist translation, a purpose exemplified in the adaptation (rather than invention) of legitimate ideological and textual strategies for translation, which make it possible to contribute to the implementation of a linguistic and social reform which seeks the eradication of gender discrimination.

Vaccine adjuvant systems: enhancing the efficacy of sub-unit protein antigens

Vaccination remains a key tool in the protection and eradication of diseases. However, the development of new safe and effective vaccines is not easy. Various live organism based vaccines currently licensed, exhibit high efficacy; however, this benefit is associated with risk, due to the adverse reactions found with these vaccines. Therefore, in the development of vaccines, the associated risk-benefit issues need to be addressed. Sub-unit proteins offer a much safer alternative; however, their efficacy is low. The use of adjuvanted systems have proven to enhance the immunogenicity of these sub-unit vaccines through protection (i.e. preventing degradation of the antigen in vivo) and enhanced targeting of these antigens to professional antigen-presenting cells. Understanding of the immunological implications of the related disease will enable validation for the design and development of potential adjuvant systems. Novel adjuvant research involves the combination of both pharmaceutical analysis accompanied by detailed immunological investigations, whereby, pharmaceutically designed adjuvants are driven by an increased understanding of mechanisms of adjuvant activity, largely facilitated by description of highly specific innate immune recognition of components usually associated with the presence of invading bacteria or virus. The majority of pharmaceutical based adjuvants currently being investigated are particulate based delivery systems, such as liposome formulations. As an adjuvant, liposomes have been shown to enhance immunity against the associated disease particularly when a cationic lipid is used within the formulation. In addition, the inclusion of components such as immunomodulators, further enhance immunity. Within this review, the use and application of effective adjuvants is investigated, with particular emphasis on liposomal-based systems. The mechanisms of adjuvant activity, analysis of complex immunological characteristics and formulation and delivery of these vaccines are considered.

Antibacterial activity of low amperage and low voltage electric current (DC)

Infection is a major clinical problem associated with the use of intravenous catheters.The efficacy of a direct electric current (10µA, 9V) via electrode-conducting carbon impregnated catheters to prevent colonisation of catheters by micro-organisms was investigated. The range of organisms susceptible to 10µA was determined by a zone of inhibition test. The catheters acting as the anode and the cathode were inserted into a nutrient agar plate inoculated with a lawn of bacteria. There was no zone of inhibition observed around the anode. Organisms susceptible to 10µA at the cathode were Staphylococcus aureus (2 strains), Staphylococcus epidermidis (5 strains), Escherichia coli and Klebsiella pneumoniae (2 strains each), and one strain of the following micro-organisms: Staphylococcus hominis, Proteus mirabilis, Pseudomonas aeruginosa and Candida albicans. The zones ranged from 6 to 16 mm in diameter according to the organisms under test. The zone size was proportional to the amperage (10 - 100 µA) and the number of organisms on the plate. Ten µA did not prevent adhesion of staphylococci to the cathode nor did it affect their growth in nutrient broth. However, it was bactericidal to adherent bacteria on the cathodal catheter and significantly reduced the number of bacteria on the catheter after 4 to 24 h application of electricity. The antimicrobial activity of low amperage electric current under anaerobic conditions and in the absence of chloride ions against bacteria attached to the surface of a current carrying electrode was also investigated.The mechanisms of the bactericidal activity associated with the cathode were investigated with S. epidermidis and S. aureus. The inhibition zone was greatly reduced in the presence of catalase. There was no zone around the cathode when the test was carried out under anaerobic conditions. Hydrogen peroxide was produced at the cathode surface under aerobic conditions, but not in the absence of oxygen. A salt-bridge apparatus was used to demonstrate further that hydrogen peroxide was produced at the cathode, and chlorine at the anode. The antimicrobial activity of low amperage electric current under anaerobic conditions and in the absence of chloride ions against bacteria attached to the surface of a current carrying electrode was also investigated. Antibacterial activity was reduced under anaerobic conditions, which is compatible with the role of hydrogen peroxide as a primary bactericidal agent of electricity associated with the cathode. A reduction in chloride ions did not significantly reduce the antibacterial activity suggesting chlorine plays only a minor role in the bactericidal activity against organisms attached to anodal electrode surfaces. The bactericidal activity of electric current associated with the cathode and H202 was greatly reduced in the presence of 50 μM to 0.5 mM magnesium ions in the test menstrum. Ten μA applied via the catheters did not prevent the initial biofilm growth by the adherent bacteria but reduced the number of bacteria in the biofilm by 2 log order aiter 24 h. The results suggested that 10 μA may prevent the colonisation of catheters by both the extra~ and intra-luminal routes. The localised production of hydrogen peroxide and chlorine and the intrinsic activity due to electric current may offer a useful method for the eradication of bacteria from catheter surfaces.