Lentiviral vector-mediated tyro sinase-related protein 2 gene transfer to dendritic cells for the therapy of melanoma

Dendritic cells (DCs) are the most potent professional antigen-presenting cells (APCs), which play a vital role in primary immune responses. Introducing genes into DCs will allow constitutive expression of the encoded proteins and thus prolong the presentation of the antigens derived therefrom. In addition, multiple and unidentified epitopes encoded by the entire tumor-associated antigen (TAA) gene may enhance T cell activation. This study demonstrated that an HIV-1-based lentiviral vector conferred efficient gene transfer to DCs. The transgene, murine tyrosinase-related protein 2 (mTRP-2), encodes a clinically relevant melanoma-associated antigen (MAA), which has been found to be a tumor rejection antigen for B16 melanoma. The transfer and proper processing of mTRP-2 in DCs, in terms of RNA transcription activity and protein expression, were verified by RT-PCR and specific antibody, respectively. Administration of mTRP-2 gene-modified DCs (DC-HR'CmT2) to C57BL/6 mice evoked strong protection against tumor challenge, for which the presence of CD4(+) and CD8(+) cells during both the priming and challenge phase was essential. In a therapy model, our results showed that four of seven mice with preestablished tumor remained tumor free for 80 days after therapeutic vaccination. Given the results shown in this study, mTRP-2 gene transfer to DCs provides a potential therapeutic strategy for the management of melanoma, especially in the early stage of the disease.

The preparation and execution of self-initiated and externally-triggered movement: A study of event-related fMRI

Studies of functional brain imaging in humans and single cell recordings in monkeys have generally shown preferential involvement of the medially located supplementary motor area (SMA) in self-initiated movement and the lateral premotor cortex in externally cued movement. Studies of event-related cortical potentials recorded during movement preparation, however, generally show increased cortical activity prior to self-initiated movements but little activity at early stages prior to movements that are externally cued at unpredictable times. In this study, the spatial location and relative timing of activation for self-initiated and externally triggered movements were examined using rapid event-related functional MRI. Twelve healthy right-handed subjects were imaged while performing a brief finger sequence movement (three rapid alternating button presses: index-middle-index finger) made either in response to an unpredictably timed auditory cue (between 8 to 24 s after the previous movement) or at self-paced irregular intervals. Both movement conditions involved similar strong activation of medial motor areas including the pre-SMA, SMA proper, and rostral cingulate cortex, as well as activation within contralateral primary motor, superior parietal, and insula cortex. Activation within the basal ganglia was found for self-initiated movements only, while externally triggered movements involved additional bilateral activation of primary auditory cortex. Although the level of SMA and cingulate cortex activation did not differ significantly between movement conditions, the timing of the hemodynamic response within the pre-SMA was significantly earlier for self-initiated compared with externally triggered movements. This clearly reflects involvement of the pre-SMA in early processes associated with the preparation for voluntary movement. (C) 2002 Elsevier Science.

Career versus motherhood? A case study describing a cognitive-existential approach to the dilemma

The present paper reports a case study concerning a professional woman in her 30s, who presented to the Occupational Health department of a metropolitan hospital with work stress stemming from accelerating work demands and marital problems related to the decision about whether to start a family or continue her career. No clinical diagnosis was warranted; however, Maslach Burnout Inventory Scores indicated a high degree of emotional exhaustion and moderate levels of depersonalisation, offset by a high sense of personal accomplishment in her work role. The client also demonstrated severe stress and moderate depression on the Depression-Anxiety-Stress Scale (DASS-21). The case was conceptualised from a combined cognitive-existential perspective. The woman's cognitions about her work, relationship, and prospective motherhood roles were identified, as well as underlying existential issues such as finding a meaning in life and a fear of being alone and unloved. Eight sessions of therapy incorporated components of cognitive and existential therapies, aimed at managing stress and improving marital adjustment. Posttreatment results showed substantial reductions in all the measures of distress, while personal accomplishment remained high. The woman and her husband decided to defer starting a family until other issues had been addressed.

Background risk in generalized expected utility theory

In this paper, it is shown that, for a wide range of risk-averse generalized expected utility preferences, independent risks are complementary, contrary to the results for expected utility preferences satisfying conditions such as proper and standard risk aversion.

Person, existence and phenomenology: remarks on the conceptions of personalism of Emmanuel Mounier

This article aims to discuss the personalism of Emmanuel Mounier, especially his views on the person and existence, and its relation to phenomenology. Mounier does not refer to the influence of phenomenology on his thoughts. However, it is possible to notice that his philosophy was strongly influenced by phenomenological ideas. Personalism is a philosophy that says a person`s value as an absolute. The absolute here is understood as a purpose that gives meaning to all the political and social organization. Human existence is the starting point and fundamental postulate of personalism. This means that there is, therefore, a priority of the existence about the human nature, understanding this as an information ""ontological definitive"". This position is a requirement of epistemological reformulation, which means, within personalism, the attempt to develop a phenomenology of existence, located between the radical objectivism of the science and subjectivism of metaphysics.

Evolutionary History of Arabidopsis thaliana Aminoacyl-tRNA Synthetase Dual-Targeted Proteins

Aminoacyl-transfer RNA (tRNA) synthetases (aaRS) are key players in translation and act early in protein synthesis by mediating the attachment of amino acids to their cognate tRNA molecules. In plants, protein synthesis may occur in three subcellular compartments (cytosol, mitochondria, and chloroplasts), which requires multiple versions of the protein to be correctly delivered to its proper destination. The organellar aaRS are nuclear encoded and equipped with targeting information at the N-terminal sequence, which enables them to be specifically translocated to their final location. Most of the aaRS families present organellar proteins that are dual targeted to mitochondria and chloroplasts. Here, we examine the dual targeting behavior of aaRS from an evolutionary perspective. Our results show that Arabidopsis thaliana aaRS sequences are a result of a horizontal gene transfer event from bacteria. However, there is no evident bias indicating one single ancestor (Cyanobacteria or Proteobacteria). The dual-targeted aaRS phylogenetic relationship was characterized into two different categories (paralogs and homologs) depending on the state recovered for both dual-targeted and cytosolic proteins. Taken together, our results suggest that the dual-targeted condition is a gain-of-function derived from gene duplication. Selection may have maintained the original function in at least one of the copies as the additional copies diverged.

Democracy versus Republic: Inclusion and Desire in Social Struggles

This paper argues that the idea of inclusion is linked to the democratic tradition rather than to the republican one. By analyzing the origins and meaning of these two concepts, the author holds that democracy is rather linked to desire and republic to will (and to the expression of desire), and concludes that, since North Atlantic political tradition has not given a key role to desire, democracy, in order to overcome the difficulties it has been encountering in all parts of the world, should take more account of desire and of the social struggles it brings to the fore.

Language, discourse and politics

After discussing the meaning of the word politics, this paper shows that there are four possible approaches to the issue of the relationships between language, discourse and politics: a) the intrinsic political nature of language; b) the relations of power between discourses and their political dimension; c) the relations of power between languages and the political dimension of their usage and; d) linguistic policies. This paper addresses only the first two of these items. Languages have an intrinsically political nature because they subject their speakers to their order. The acts of silencing operationalized in discourse manifest a relation of power. The spread of discourses in the social space is also subject to the order of power. The use of language may be the space of pertinence, but is also that of exclusion, separation and even the elimination of the other. Therefore, language is not a neutral communication tool, but it is permeated by politics, by power. Because of the dislocations that it produces, literature is a form of swindling language, unveiling the powers that are imprinted on it.

Contextual politics of service delivery reforms: Lessons from Delhi, Mexico city and Sao Paulo comparison

Little attention has been given to the contextual politics of service delivery reforms. By focusing on cases of reform in the healthcare sector and, to a lesser extent, in the main policies in the social service sector in India, Mexico and Brazil, this article explores two dimensions of analysis which have enormous relevance in understanding the reach and effectiveness of service delivery reforms: (1) the historical timing of reforms and sectorial baselines, and (2) the degree and institutional locus of local discretion in policy. Findings show that depending on both dimensions, there is an extraordinary variation as to the degree, interests involved and meaning of changes which, in theory, correspond to these countries` commitment to the service delivery reforms, However, consideration of the contextual politics is relevant not for the sake of diversity but for the similarities that this diversity reveals, pointing to underlying analytic dimensions that receive attention in this article.

Molecular epidemiology: A multidisciplinary approach to understanding parasitic zoonoses

Sound application of molecular epidemiological principles requires working knowledge of both molecular biological and epidemiological methods. Molecular tools have become an increasingly important part of studying the epidemiology of infectious agents. Molecular tools have allowed the aetiological agent within a population to be diagnosed with a greater degree of efficiency and accuracy than conventional diagnostic tools. They have increased the understanding of the pathogenicity, virulence, and host-parasite relationships of the aetiological agent, provided information on the genetic structure and taxonomy of the parasite and allowed the zoonotic potential of previously unidentified agents to be determined. This review describes the concept of epidemiology and proper study design, describes the array of currently available molecular biological tools and provides examples of studies that have integrated both disciplines to successfully unravel zoonotic relationships that would otherwise be impossible utilising conventional diagnostic tools. The current limitations of applying these tools, including cautions that need to be addressed during their application are also discussed.(c) 2005 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

The Gothic scene of international relations: ghosts, monsters, terror and the sublime after September 11

Accepting Furet’s claim that events acquire meaning and significance only in the context of narratives, this article argues that a particular type of international relations narrative has emerged with greater distinction after the traumatic experience of September 11: the gothic narrative. In a sense the political rhetoric of President Bush marks the latest example of America’s fine tradition in the gothic genre that began with Edgar Allan Poe and Nathaniel Hawthorne and extends through Henry James to Stephen King. His discourse of national security, it will be shown, assumes many of the predicates of gothic narratives. The gothic scenes evoked by Bush as much as Poe involve monsters and ghosts in tenebrous atmospheres that generate fear and anxiety, where terror is a pervasive tormentor of the senses. Poe’s narratives, for example, turn on encounters with dark, perverse, seemingly indomitable, forces often entombed in haunted houses. Similarly, Bush’s post-September 11 narratives play upon fears of terrorists and rogue states who are equally dark, perverse and indomitable forces. In both cases, ineffable and potently violent and cruel forces haunt and terrorise the civilised, human world.

The role of micro-anchor devices in medial canthopexy

Telecanthus, the lateral displacement of the medial canthus, can be a congenital deformity or can occur after facial trauma or tumor resection. Treatment of telecanthus remains a challenge for plastic surgeons. For proper correction, it is necessary to shift the medial canthus medially, fixing its tendon to the bone. The ideal technique would allow easy, safe, and stable fixation of the tendon, permit a unilateral approach with minimal incisions, and be cost-effective. The purpose of this study was to evaluate the feasibility and results (immediate and long-term) of medial telecanthus repair using ipsilateral titanium microanchor fixation. Nine patients, 7 with unilateral telecanthus and 2 with bilateral telecanthus, underwent ipsilateral canthopexy involving a microanchor device. Anthropometric measurements of the orbital regions were taken before, immediately after, and at 1 year after surgery. Data for the affected sides were compared with those for the unaffected sides, and the evolution of those values was assessed throughout the 1-year follow-up period. For all patients, the final values were lower than those initially obtained. At 1 year after surgery, the intercanthal distance was reduced to age-adjusted normal values in all cases. On the operated side, stable improvement was observed in terms of the distance from the medial canthus to the midline, although some degree of recurrence was noted in most of the patients. The use of a microanchor system for medial canthopexy can be considered an easily performed and effective option for treating canthal dystopia, especially when an ipsilateral approach is preferred.

Meta-analysis of infrapopliteal angioplasty for chronic critical limb ischemia

Background: Percutaneous transluminal angioplasty has been used with increasing frequency in the treatment of infrainguinal arterial occlusive disease. This meta-analysis aimed to assess the middle-term outcomes after crural angioplasty in patients with chronic critical limb ischemia and compare results with a meta-analysis of popliteal-to-distal vein bypass graft. Methods: Data were retrieved from 30 articles published from 1990 through 2006 (63% of articles published between 2000 and 2006). All studies used survival analysis, reported a 12-month cumulative rate of patency or limb salvage, and included at least 15 infrapopliteal angioplasties. The outcome measures were immediate technical success, primary and secondary patency, limb salvage, and patient survival. Data from life-tables, survival curves, and texts were used. Results. The pooled estimate of success was 89.0% +/- 2.2% for immediate technical result. Results at 1 and 36 months were 77.4% +/- 4.1% and 48.6% +/- 8.0% for primary patency, 83.3% +/- 1.4% and 62.9% +/- 11.0% for secondary patency, 93.4% +/- 2.3% and 82.4% +/- 3.4% for limb salvage, and 98.3% +/- 0.7% and 68.4% +/- 5.5% for patient survival, respectively. Studies with >75% of the limbs with tissue loss fared worse than their respective comparative subgroup for technical success and patency but not for limb salvage or survival. No publication bias was detected. Conclusion: The technical success and subsequent durability of crural angioplasty are limited compared with bypass surgery, but the clinical benefit is acceptable because limb salvage rates are equivalent to bypass surgery. Further studies are necessary to determine the proper role of infrapopliteal angioplasty.

Mammaplasty with Inferior Pedicle Flap After Massive Weight Loss

After massive weight loss, one of the stigmas that afflict women is the remaining deformity of the breasts which become flaccid and ptotic, with an absent or flat upper pole. The authors propose the use of a well-established mammaplasty technique to fill the upper pole, reshape the breast cone, and correct ptosis with nipple-areola complex (NAC) repositioning. A total of 16 patients were analyzed; all underwent gastroplasty between 18 and 24 months prior to mammaplasty. The mean age was 41.6 years (range = 26-62) and the mean BMI previous to the mammaplasty was 29.2 kg/m(2) (range = 24.9-38.9). The technique included a dermo-lipo glandular flap pedicled on the inframammary fold (IMF) together with a superior flap containing the NAC. All patients who underwent surgery were satisfied with the outcomes since a more aesthetic breast shape was achieved, with projection of the upper pole and correction of ptosis. Adverse events included dehiscence at the junction point of the flaps in the inframammary fold, which resolved with secondary-intention wound healing in three patients; partial necrosis of the areola in one patient; epidermolysis in one of the NACs in one patient; and infection in one of the breasts in one patient, which resolved with proper antibiotic therapy. When compared to the current mammaplasty techniques performed in formerly obese patients, this is a good surgical option because it uses tissues adjacent to the breast itself and does not require silicone prosthesis for breast augmentation. The patients reported increased self-esteem and improvement in their quality of life.

Family advocacy roles and highly dependent residents in nursing homes

A developing critique has questioned the practical utility of user rights policy initiatives for highly dependent residents of nursing homes. This paper seeks to extend this critique to the advocacy roles that families have been accorded within the policy initiatives, The discussion is based on a qualitative research study of family participation in six aged care units, The paper argues that the capacity of families to act as advocates for highly dependent nursing home residents is is limited by the their weak position within the organisations and the complexity of their relations with staff It questions both the applicability and the appropriateness of rights models which do not take sufficient account of the structure and meaning of care.