bluuebunny/crossref_metadata_2025 huggingface dataset:
Playing as Adaptation? Layered Selfhood and Self-regard in Cultural Contexts
Authors: Zhao Guoping
Published: March 2005

The current paradigm shift from realism and humanism to social constructionism and postmodernism has tremendous implications for social sciences, especially for psychology. The idea that not only our knowledge, but also our self, emotions and cognitions are constructed by society and culture is embraced by some cross-cultural and cultural psychologists and postmodernists. While this stance attempts to integrate culture and psychology, it depreciates the part of the self that can stand apart from culture and society and therefore be shared among humankind. This paper proposes a layered model of selfhood to incorporate both universal and existential human experience and the influence of culture and society. Heine, Lehman, Markus and Kitayama’s (1999) cross-cultural study of self-regard serves as an exemplar of the constructionist approach and their data are reanalyzed using the proposed model of selfhood. The notion of ‘play’ is introduced to understand the dynamics at the interface between cultural regulations and individuals. This paper also explores the cultural norms of East Asia and America.
Masking as Ludic Practice of Selfhood in Japan
Authors: Köpping Klaus-Peter
Published: March 2005

At least since the work of Durkheim and Mauss on the primacy of social relations for the establishing of mental categories, the idea of self seemed only relevant insofar as it was perceived as a social category. This essay addresses the question of the essential or phenomenal givenness of selfhood, as proposed in Zhao’s (2005) paper, by tracing the conceptual strife in anthropological theories from Marcel Mauss onwards, pointing to the problems associated with abstract categories which become only meaningful as well as observable through concentration on the performativity of the social. To concretize the abstract issue, the essay concentrates on the notion of the mask as it surfaces through ritual and theatrical performances in Japan. As Japanese behavioural codes have also become the mainstay of comparative references for western notions of individuality, the essay presents a case-study of masked ritual performance in order to show the embodiment of abstract notions in ritual play as well as in theatrical staging. Following this case study the essay finishes with questions about the ludic nature of theatrical, ritual as well as social enactments of self in Japanese cultural practices, trying to connect these to the theoretical system of the ludic, as proposed by Roger Caillois (1958).
Domination, Subordination and the Dialogical Self: Identity Development and the Politics of ‘Ideological Becoming’
Authors: Tappan Mark B.
Published: March 2005

In this paper I present an approach to understanding the dialogical self that considers the role that social, cultural and institutional dynamics of domination and subordination, and structures of power of privilege, play in the development of identity. To accomplish this I expand Penuel and Wertsch’s (1995) ‘mediated action’ approach to identity development to include a dialogical process of what Mikhail Bakhtin (1981) calls ‘ideological becoming’. Using the Autobiography of Malcolm X as an illustrative example, I argue that the development of Malcolm’s identity, via the process of ideological becoming, is influenced in profound ways by his experience of subordination and oppression, and his lack of power and privilege, growing up as a black man in the United States in the first half of the 20th century. Thus the ‘ politics of ideological becoming’ refers to the degree to which the process of identity formation is necessarily different for persons from different social locations, who stand in different relationship to structures and systems of power, privilege and authority.
Extending the Boundaries of the Dialogical Self: Speaking from within the Feminist Perspective
Authors: Barcinski Mariana , Kalia Vrinda
Published: March 2005

The purpose of this paper is to explore the ways in which feminist theory can contribute to the construction of an alternative and more inclusive account of the process of identity development than the one proposed by dialogical accounts. Focusing on Anzaldua’s (1987) concept of mestiza and on Lugones’ (1994) concept of curdling, the paper proposes an approach to identity formation that is sensitive to the dialogicality of people’s experiences. This move away from the notion of purity and truth-seeking psychological accounts should acknowledge the fundamental hybridity of lived experiences.
Institutional Economics and Planning Theory: A Partnership between Ostriches?
Authors: Moulaert Frank
Published: March 2005

Institutional economics is not a homogeneous field, but a pluralist family of approaches, all analysing institutional aspects of economic development and organization. A distinction is usually made between New Institutionalism (evolutionary economics, regulation theory and various offshoots of ‘old’ US institutionalism) and New Institutional Economics (NIE). This article examines the principal theoretical underpinnings of these currents and assesses their potential to enrich planning theory, in particular institutional planning and land-use planning theory. The author warns against injudicious marriages, especially if future spouses behave as ostriches, seeking to avoid ontological incompatibilities.
The Political Relevance of Planners’ Analysis: The Case of a Parliamentary Standing Committee
Authors: Sager Tore , Ravlum Inger-Anne
Published: March 2005

The article examines and confirms the hypothesis that political decision makers gather information and do not use it; ask for more information and ignore it; make decisions first and look for relevant information afterwards; and, collect and process a great deal of information that has little or no direct relevance to decisions. The results are based on interviews with members of the Norwegian national assembly’s Standing Committee on Transport and Communications. In three parliamentary periods, members were interviewed about their use of results from analytic planning models evaluating the projects and strategies of three consecutive road and transport plans. It is studied how the attitudes of the politicians towards the analytic results change as the planners supply increasingly advanced means-ends models.
Transformation of Some Aspects of the Local Mode of Regulation in Sweden
Authors: Khakee Abdul
Published: March 2005

This article analyses one dimension of the local mode of regulation in Sweden, namely national laws and institutions steering local urban planning and housing. Regulation theoretic analyses have traditionally focused on ‘extralocal’ political and economic factors. This article attempts to explain the concrete construction of regulatory mechanism at the local level as a part of a broader regulation process. It suggests that there is a strong connection between economic shifts and shifts in urban policy in Sweden. It rejects, however, the idea of the state serving capital accumulation à la carte.
Applying Lacanian Insight and a Dash of Derridean Deconstruction to Planning’s ‘Dark Side’
Authors: Allmendinger Phil , Gunder Michael
Published: March 2005

The critique of planning’s ‘dark’ side has been a theme of both modern and postmodern perspectives. While a great deal of anecdotal and empirical evidence exists that highlights how planning can be, and has been, used for nefarious ends there are few theoretical insights or understandings of the role of different actors, institutions or processes. This article provides a critical analysis of the notion of ‘dark side’ from a Lacanian and Derridean perspective. A short case study of the use of planning for what would broadly be regarded as ‘dark’ ends highlights a number of issues, particularly through engagement with Lacanian theory, which provides a useful theoretical framework for further research into the misuse of planning.
Meier, Miracle and Multiple Attestation
Authors: Eve Eric
Published: March 2005

The use of criteria in historical Jesus research gives the enterprise an appearance of scientific objectivity that may be deceptive. A particular case in point is the use of multiple attestation to establish the near certainty that the historical Jesus was a healer and exorcist (as, for example, J.P. Meier argues). Logically, there is little reason why multiple attestation alone should indicate historical reliability, and there may not be as many useful independent sources for Jesus’ miracles as Meier supposes. Jesus may well have been a healer and exorcist, but if so, this needs to be established on other grounds.
Presuppositions and Procedures in the Study of the ‘Historical Jesus’: Or, Why I Decided Not to be a ‘Historical Jesus’ Scholar
Authors: Willitts Joel
Published: March 2005

This article provides a detailed description of the presuppositions and procedures of a representative group of six scholars currently contributing to the study of the ‘historical Jesus’. The intention of the study was to draft a ‘handbook’, a ‘recipe’, of the best methods and the surest presuppositions for achieving the result of a solid historical conclusion about Jesus. What resulted from the project was not what had been hoped. In fact, what resulted was a deep scepticism about the quest, at least as it is currently being conducted. Though, admittedly, not offering solutions, this article seeks to raise questions about the real potential and usefulness of any quest for the so-called ‘historical Jesus’.
‘Rooted in Detachment’: Transfiguration as Narrative, Worship and Community of Faith
Authors: Stevenson Kenneth
Published: March 2005

The Transfiguration is recorded in all three synoptic gospels, and points the onlookers towards the cross. The article looks at these narratives, with their variations, and then examines the way in which expositors and preachers, patristic, medieval and modern, have applied the Transfiguration to Christian living. Important are the two quite distinct ways in which the narrative has been used liturgically, in the Latin West, originally as a feature of Lenten preaching, and in the East as a festival in its own right on August 6th. Drawing the two traditions of interpretation and worship together, it is possible to see fresh ways of understanding the impact of the Transfiguration on the Church’s self-understanding: the tension between continuity and discontinuity; the transformation of the three uncomprehending apostles; and the hidden but mobile character of the community of faith. The Transfiguration emerges as a truth that illuminates Christian discipleship at its most profound.
The Church of Jesus Christ: An Introduction
Authors: Beintker Michael
Published: March 2005

This paper focuses on those points in the study The Church of Jesus Christ which may be important for dialogue on ecclesiological questions between the Community of Protestant Churches in Europe (CPCE) and the Anglican Churches in Europe. After a short account of the process of coming into being of this study, it summarizes its most important basic theological insights. Then it focuses on the questions of ministry and episkope and concludes with some remarks on the understanding of church unity in the context of the document.
Nurses: The agenda for change
Authors: Fernandez J. , Greening M.
Published: March 2005

This paper highlights the level of expertise and ability of nurses to change the clinical approach of a multi-disciplinary team in service provision. This is in relation to improving a drug clinic’s outlook and care programme approach for alcohol. The senior nurses saw a gap in service provision for alcohol and, through conducting an audit and further qualitative research, they were able to identify which clinical approaches needed updating and ‘finetuning’ in the London borough of Islington, producing updated guidelines for the clinic. The results showed that there was a cohort of clients attending for treatment who had a dual problem with alcohol and drugs. This was often missed on the initial assessment form. From the audit and further local research, the assessment was changed, which improved the identification of an alcohol dependency so that an appropriate care plan could be draw up. From the qualitative study there was also a perceived resistance from the client group to address their alcohol dependency, and on being breathalysed when receiving a script for methadone. It was felt that the reasoning for this could be the clinical procedure was not being explained. However, what was identified from the clinical research was that this reasoning from the client group was unjustified with clear clinical reasons for this procedure being given to the client from the nursing staff. Importantly, this paper aims to illustrate the clinical development role nurses can play in improving care for services through evidence-based practice and development of updated guidelines. The guidelines produced from this work have, in turn, ensured better care for clients of the service.
Ethical and methodological issues in palliative care studies
Authors: Seymour Jane , Payne Sheila , Reid David , Sargeant Anita , Skilbeck Julie , Smith Paula
Published: March 2005

This paper reports on the experiences of a nursing-led research group, ‘The Palliative and End of Life Care Research Group’, within the School of Nursing and Midwifery at the University of Sheffield. There is a long tradition of research in palliative care in which nurses have played an important role and currently opportunities to conduct research in palliative care are expanding. Nurses face a number of ethical and methodological challenges in conducting palliative care research, many of which extend beyond individual research conduct. Drawing on practical examples in each case, this paper explores the following themes: issues involved in raising participation and recruitment to studies of palliative care; how the topics of palliative and end-of-life care are introduced and explored with participants; what ‘special’ needs participants have in palliative care research; interpersonal issues in conducting palliative care research; and providing support and supervision to researchers.
Care of the dying stroke patient in the acute setting
Authors: Rogers Angie , Addington-Hall Julia
Published: March 2005

Stroke is the third most common cause of death in England and Wales, accounting for 11% of all deaths. Predictors of early mortality following stroke have been known for over a century and include a history of stroke, age, disorientation to time and place and level of consciousness. To date, hospices and specialist palliative care services have focused on caring for terminally ill cancer patients, with 95% of their patients in 2000–2001 having cancer. However it has been acknowledged since its inception that the practices and principles of palliative care may be relevant to those dying from other conditions. Recently there has been a growing interest in palliative care for non-cancer diagnosis and increasing recognition that palliative care should be provided on the basis of need rather than diagnosis. Despite the high levels of mortality following stroke, to date, little has been published about dying from stroke. In this study we report on a prospective qualitative study of the nursing and medical care received by dying stroke patients.
Promoting end-of-life care in nursing homes using an ‘integrated care pathway for the last days of life’
Authors: Hockley Jo , Dewar Belinda , Watson Julie
Published: March 2005

The purpose of this study was to promote quality end-of-life care in eight independent nursing homes using an ‘integrated care pathway (ICP) for the last days of life’ document. Action research methodology underpinned the design of this study in order to promote collaboration between staff in the nursing homes and the research team, empower staff in the practice of quality end-of-life care, and promote sustainable development of end-of-life care once the study finished. Considerable barriers within the nursing home context highlighted initial difficulties. This is reported elsewhere (Watson et al., in press) (Bridges Initiative, 2004). However, key champions appointed in each nursing home and their subsequent support was a major part of facilitating the ICP implementation. This paper reports the qualitative analysis from the summative evaluation of the study. One overarching pattern of ‘dying being more central to care in the nursing homes’ emerged as a result of the study; five themes that contributed to this shift were: greater ‘openness’ around death and dying; recognising dying and taking responsibility; better ‘teamwork’; critically using palliative care knowledge to influence practice; more meaningful communication.
Ultrasound in the Investigation of Pelvic Pain
Authors: Dixon Anne-Marie
Published: March 2005

An ultrasound examination is commonly requested during the evaluation of women presenting for investigation of pelvic pain. This paper reviews the common causes of pelvic pain describing the associated clinical signs and symptoms, the typical ultrasound appearances and the role of ultrasound in patient management.
Incorporating 3D and 4D Ultrasound into Clinical Practice
Authors: Smith Alison , Chudleigh Trish , Maxwell Darryl
Published: March 2005

3D ultrasound has been slow to make significant impact in clinical practice. In a large part, this is because 2D ultrasound is of such superior quality that sonographers have not seen any gain in adopting the new technology. More recently, however, diverse application of 3D technology has taken place in many branches of medicine, with obstetrics and gynaecology at the forefront. Several manufacturers now produce machines of remarkable sophistication and utility. Hardware and software have been integrated to allow the release of information from the ultrasound examination that has hitherto not been possible. In addition, virtual real time 3D images (4D ultrasound) have captured the imagination of both public and media. We report our preliminary clinical experience with 3 and 4D ultrasound in a limited clinical environment. While not suitable for wide scale application at present, we believe this technology has inherent advantages that will secure its clinical role and that this role will widen rapidly in the near future.
Picture Archival and Communications System (PACS) and the Ultrasound Department
Authors: Cunningham Cliona
Published: March 2005

With the increase in the speed of computers and a reduction in the cost of computer hardware, PACS the electronic method acquiring and storing diagnostic images is a more attractive commodity. PACS is a network of computer systems, which must integrate well to improve efficiency. This review describes the various components of PACS and discusses the requirements of the ultrasound user.
Investigating the Fetal Circulation: Liver, Renal and Intracranial Vasculature
Authors: Loughna Pam
Published: March 2005

Whilst interrogation of the umbilical artery (and vein) using Doppler has been a standard part of fetal assessment for over 20 years, the role of other vessels amenable to study has been subject to a slower development. Initial interest in other vessels concentrated on fetal assessment in conditions where fetal growth was sub-optimal, but as the use of ultrasound equipment with colour and pulsed wave Doppler has become more commonplace, so have the applications become wider. Examination of the fetal circulation now has a role in detection of aneuploidy, risk assessment in monochorionic twins, noninvasive assessment of fetal anaemia and the investigation of structural malformations. Whilst there is no indication for routine Doppler examination in obstetric ultrasound, there are many specific indications, some of which are only relevant to tertiary level scans. However, application of Doppler in the assessment of suspected anomalies is appropriate in the routine setting in many situations. The techniques for examining blood flow in different fetal vessels are essentially the same as those employed for the umbilical artery. The fetus needs to be quiescent. The direction of flow in the vessel should be as near vertical to the transducer as possible, with the sampling gate being small enough to accommodate the vessel. Angle correction is not essential for assessment of resistance, but is required for absolute velocities. Care should be taken to avoid excess pressure with the transducer, particularly on the fetal head, as this does affect blood flow.
Case Report: Early Fetoscopic Management of Monochorionic Twin Pregnancy Complicated by Amniotic Band Syndrome and Twin to Twin Transfusion
Authors: Holsbeke Van C. ,   Christiaens,   Stoutenbeek,   Vandenbussche
Published: March 2005

We report a case where discordant amniotic band syndrome was diagnosed in a monochorionic twin pregnancy in the early second trimester of pregnancy. Pregnancy was also complicated by twin-to-twin transfusion syndrome. Therapeutic options were limited because of the severity of the amniotic strings and the twin transfusion syndrome. We offered selective feticide by bipolar coagulation of the umbilical cord of the affected fetus. This was performed successfully and also converted the transfusion syndrome, leading to the term birth of a healthy baby, with an 'aplasia cutis'-like skin lesion on the skull. The differential diagnostic and therapeutic steps in this complex case are discussed, as well as the possible relationship between the skin lesion and the fetoscopic intervention.
Inhibition of CD4+25+ T regulatory cell function implicated in enhanced immune response by low-dose cyclophosphamide
Authors: Lutsiak M. E. Christine , Semnani Roshanak T. , De Pascalis Roberto , Kashmiri Syed V. S. , Schlom Jeffrey , Sabzevari Helen
Published: March 2005

Regulatory T cells (TREGs) control the key aspects of tolerance and play a role in the lack of antitumor immune responses. Cyclophosphamide (CY) is a chemotherapeutic agent with a dose-dependent, bimodal effect on the immune system. Although a previous study demonstrated that CY reduces the number of TREGs, the mechanism involved in this process has yet to be defined. In this report, it is established that low-dose CY not only decreases cell number but leads to decreased functionality of TREGs. CY treatment enhances apoptosis and decreases homeostatic proliferation of these cells. Expression of GITR and FoxP3, which are involved in the suppressive activity of TREGs, is down-regulated after CY administration, though the level of expression varies depending on the time studied. This is the first report demonstrating that CY, in addition to decreasing cell number, inhibits the suppressive capability of TREGs. The relevance of the loss of suppressor functionality and the changes in gene expression are further discussed.
Triggering of OX40 (CD134) on CD4+CD25+ T cells blocks their inhibitory activity: a novel regulatory role for OX40 and its comparison with GITR
Authors: Valzasina Barbara , Guiducci Cristiana , Dislich Heidrun , Killeen Nigel , Weinberg Andrew D. , Colombo Mario P.
Published: March 2005

OX40 (CD134) is a member of the tumor necrosis factor (TNF) receptor family that is transiently expressed on T cells after T-cell receptor (TCR) ligation. Both naive and activated CD4+CD25+ regulatory T cells (T reg's) express OX40 but its functional role has not been determined. Since glucocorticoid-induced tumor necrosis factor receptor (GITR), a related TNF receptor family member, influences T reg function, we tested whether OX40 might have similar effect. Triggering either GITR or OX40 on T reg's using agonist antibodies inhibited their capacity to suppress and restored effector T-cell proliferation, interleukin-2 (IL-2) gene transcription and cytokine production. OX40 abrogation of T reg suppression was confirmed in vivo in a model of graft-versus-host disease (GVHD). In a fully allogeneic C57BL/6>BALB/c bone marrow transplantation, GVHD was lethal unless T reg's were cotransferred with the bone marrow and effector T cells. Strikingly, T reg suppression of GVHD was abrogated either by intraperitoneal injection of anti-OX40 or anti-GITR monoclonal antibodies (mAbs) immediately after transfer, or by in vitro pretreatment of T reg's with the same mAbs before transfer. Cumulatively, the results suggest that in addition to controlling memory T-cell numbers, OX40 directly controls T reg–mediated suppression.
Endothelial tetraspanin microdomains regulate leukocyte firm adhesion during extravasation
Authors: Barreiro Olga , Yáñez-Mó María , Sala-Valdés Mónica , Gutiérrez-López María Dolores , Ovalle Susana , Higginbottom Adrian , Monk Peter N. , Cabañas Carlos , Sánchez-Madrid Francisco
Published: March 2005

Tetraspanins associate with several transmembrane proteins forming microdomains involved in intercellular adhesion and migration. Here, we show that endothelial tetraspanins relocalize to the contact site with transmigrating leukocytes and associate laterally with both intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). Alteration of endothelial tetraspanin microdomains by CD9–large extracellular loop (LEL)–glutathione S–transferase (GST) peptides or CD9/CD151 siRNA oligonucleotides interfered with ICAM-1 and VCAM-1 function, preventing lymphocyte transendothelial migration and increasing lymphocyte detachment under shear flow. Heterotypic intercellular adhesion mediated by VCAM-1 or ICAM-1 was augmented when expressed exogenously in the appropriate tetraspanin environment. Therefore, tetraspanin microdomains have a crucial role in the proper adhesive function of ICAM-1 and VCAM-1 during leukocyte adhesion and transendothelial migration.
Bone marrow mesenchymal stem cells induce division arrest anergy of activated T cells
Authors: Glennie Sarah , Soeiro Inês , Dyson Peter J. , Lam Eric W.-F. , Dazzi Francesco
Published: March 2005

It has been shown that mesenchymal stem cells (MSCs) induce T cells to become unresponsive. We characterized the phenotype of these T cells by dissecting the effect of MSCs on T-cell activation, proliferation, and effector function. For this purpose, an in vitro murine model was used in which T-cell responses were generated against the male HY minor histocompatibility antigen. In the presence of MSCs, the expression of early activation markers CD25 and CD69 was unaffected but interferon-γ (IFN-γ) production was reduced. The inhibitory effect of MSCs was directed mainly at the level of cell proliferation. Analysis of the cell cycle showed that T cells, stimulated in the presence of MSCs, were arrested at the G1 phase. At the molecular level, cyclin D2 expression was profoundly inhibited, whereas p27kip1 was up-regulated. When MSCs were removed from the cultures and restimulated with the cognate peptide, T cells produced IFN-γ but failed to proliferate. The addition of exogenous interleukin-2 (IL-2) did not restore proliferation. MSCs did not preferentially target any T-cell subset, and the inhibition was also extended to B cells. MSC-mediated inhibition induces an unresponsive T-cell profile that is fully consistent with that observed in division arrest anergy.
MBEToolbox: a Matlab toolbox for sequence data analysis in molecular biology and evolution
Authors: Cai James J , Smith David K , Xia Xuhua , Yuen Kwok-yung
Published: March 2005

Background

MATLAB is a high-performance language for technical computing, integrating computation, visualization, and programming in an easy-to-use environment. It has been widely used in many areas, such as mathematics and computation, algorithm development, data acquisition, modeling, simulation, and scientific and engineering graphics. However, few functions are freely available in MATLAB to perform the sequence data analyses specifically required for molecular biology and evolution.

Results

We have developed a MATLAB toolbox, called MBEToolbox, aimed at filling this gap by offering efficient implementations of the most needed functions in molecular biology and evolution. It can be used to manipulate aligned sequences, calculate evolutionary distances, estimate synonymous and nonsynonymous substitution rates, and infer phylogenetic trees. Moreover, it provides an extensible, functional framework for users with more specialized requirements to explore and analyze aligned nucleotide or protein sequences from an evolutionary perspective. The full functions in the toolbox are accessible through the command-line for seasoned MATLAB users. A graphical user interface, that may be especially useful for non-specialist end users, is also provided.

Conclusion

MBEToolbox is a useful tool that can aid in the exploration, interpretation and visualization of data in molecular biology and evolution. The software is publicly available at http://web.hku.hk/~jamescai/mbetoolbox/ and http://bioinformatics.org/project/?group_id=454.
Human immunodeficiency virus type 1 (HIV-1) proviral DNA load in purified CD4+ cells by LightCycler® Real-time PCR
Authors: Kabamba-Mukadi Benoît , Henrivaux Philippe , Ruelle Jean , Delferrière Nicole , Bodéus Monique , Goubau Patrick
Published: March 2005

Background

The human immunodeficiency virus type 1 (HIV-1) proviral DNA persists in infected cells, even after prolonged successful HAART. In the present study, a relative quantification assay of HIV-1 proviral DNA by LightCycler® real-time PCR based on SYBR Green I detection was developed in comparison to the number of purified CD4+ cells as estimated by the quantification of the β-globin gene.

Methods

The ability of the designed gag primers to quantify HIV-1 Group M and the PCR efficiency were assessed on HIV-1 reference isolate subtypes A, B, C and D. The 8E5 cell line containing a single defective copy of HIV-1 proviral DNA was used as a standard for both the HIV-1 target gene and the β-globin reference gene. The assay was applied on thirty consecutive patient samples received for RNA viral load determinations and on retrospective samples from fifteen patients undergoing 2 years of structured treatment interruption (STI).

Results

The lower limit of quantification was 50 HIV-1 DNA proviral copies per CD4+ cell sample. The dynamic range was from 50 to 106 HIV-1 DNA copies per CD4+ cell sample with intra- and inter-assay coefficients of variability ranging from 3.1% to 37.1%. The β-globin reference gene was quantified down to a limit of 1.5 pg of DNA/μl (approximately 5 cells) with intra- and interassay coefficients of variability ranging from 1.8% to 21%. DNA proviral load varies widely among HIV-1 infected patients. Proviral load and plasma viral load rebound were high in STI patients who took longer to achieve an undetectable plasma viral load under therapy. A statistically significant correlation was observed between DNA proviral load and RNA steady state viral load in STI patients (p-value = 0,012).

Conclusion

We have developed a fast, sensitive and specific relative quantification assay of HIV-1 proviral DNA in purified CD4+ cells. The assay enables the monitoring of HIV-1 proviral load, which may be useful to monitor therapy efficacy especially in patients with undetectable plasma RNA viral load, and allows the exploration of viral reservoirs.
Surgical revascularization versus amputation for peripheral vascular disease in dialysis patients: a cohort study
Authors: Logar Christine M , Pappas Lisa M , Ramkumar Nirupama , Beddhu Srinivasan
Published: March 2005

Background

Surgical treatment of peripheral vascular disease (PVD) in dialysis patients is controversial.

Methods

We examined the post-operative morbidity and mortality of surgical revascularization or amputation for PVD in a retrospective analysis of United States Renal Data System. Propensity scores for undergoing amputation were derived from a multivariable logistic regression model of amputation.

Results

Of the Medicare patients initiated on dialysis from Jan 1, 1995 to Dec 31, 1999, patients underwent surgical revascularization (n = 1,896) or amputation (n = 2,046) in the first 6 months following initiation of dialysis were studied. In the logistic regression model, compared to claudication, presence of gangrene had a strong association with amputation [odds ratio (OR) 19.0, 95% CI (confidence interval) 13.86–25.95]. The odds of dying within 30 days and within1 year were higher (30 day OR: 1.85, 95% CI: 1.45–2.36; 1 yr OR: 1.46, 95% CI: 1.25–1.71) in the amputation group in logistic regression model adjusted for propensity scores and other baseline factors. Amputation was associated with increased odds of death in patients with low likelihood of amputation (< 33rd percentile of propensity score) and moderate likelihood of amputation (33rd to 66th percentile) but not in high likelihood group (>66th percentile). The number of hospital days in the amputation and revascularization groups was not different.

Conclusion

Amputation might be associated with higher mortality in dialysis patients. Where feasible, revascularization might be preferable over amputation in dialysis patients.
Crystal structure of THEP1 from the hyperthermophile Aquifex aeolicus: a variation of the RecA fold
Authors: Roßbach Michael , Daumke Oliver , Klinger Claudia , Wittinghofer Alfred , Kaufmann Michael
Published: March 2005

Background

aaTHEP1, the gene product of aq_1292 from Aquifex aeolicus, shows sequence homology to proteins from most thermophiles, hyperthermophiles, and higher organisms such as man, mouse, and fly. In contrast, there are almost no homologous proteins in mesophilic unicellular microorganisms. aaTHEP1 is a thermophilic enzyme exhibiting both ATPase and GTPase activity in vitro. Although annotated as a nucleotide kinase, such an activity could not be confirmed for aaTHEP1 experimentally and the in vivo function of aaTHEP1 is still unknown.

Results

Here we report the crystal structure of selenomethionine substituted nucleotide-free aaTHEP1 at 1.4 Å resolution using a multiple anomalous dispersion phasing protocol. The protein is composed of a single domain that belongs to the family of 3-layer (α/β/α)-structures consisting of nine central strands flanked by six helices. The closest structural homologue as determined by DALI is the RecA family. In contrast to the latter proteins, aaTHEP1 possesses an extension of the β-sheet consisting of four additional β-strands.

Conclusion

We conclude that the structure of aaTHEP1 represents a variation of the RecA fold. Although the catalytic function of aaTHEP1 remains unclear, structural details indicate that it does not belong to the group of GTPases, kinases or adenosyltransferases. A mainly positive electrostatic surface indicates that aaTHEP1 might be a DNA/RNA modifying enzyme. The resolved structure of aaTHEP1 can serve as paradigm for the complete THEP1 family.
An assessment of food supplementation to chronically sick patients receiving home based care in Bangwe, Malawi : a descriptive study
Authors: Bowie Cameron , Kalilani Linda , Marsh Reg , Misiri Humphrey , Cleary Paul , Bowie Claire
Published: March 2005

Background

The effect of food supplementation provided by the World Food Programme to patients and their families enrolled in a predominantly HIV/AIDS home based care programme in Bangwe Malawi is assessed.

Methods

The survival and nutritional status of patients and the nutritional status of their families recruited up to six months before a food supplementation programme started are compared to subsequent patients and their families over a further 12 months.

Results

360 patients, of whom 199 died, were studied. Food supplementation did not improve survival but had an effect (not statistically significant) on nutritional status. Additional oil was given to some families; it may have improved survival but not nutritional status.

Conclusion

Food supplementation to HIV/AIDS home based care patients and their families does not work well. This may be because the intervention is too late to affect the course of disease or insufficiently targeted perhaps due to problems of distribution in an urban setting. The World Food Programme's emphasis on supplementary feeding for these families needs to be reviewed.
Therapeutic targets for HIV-1 infection in the host proteome
Authors: Liang Winnie S , Maddukuri Anil , Teslovich Tanya M , de la Fuente Cynthia , Agbottah Emmanuel , Dadgar Shabnam , Kehn Kylene , Hautaniemi Sampsa , Pumfery Anne , Stephan Dietrich A , Kashanchi Fatah
Published: March 2005

Background

Despite the success of HAART, patients often stop treatment due to the inception of side effects. Furthermore, viral resistance often develops, making one or more of the drugs ineffective. Identification of novel targets for therapy that may not develop resistance is sorely needed. Therefore, to identify cellular proteins that may be up-regulated in HIV infection and play a role in infection, we analyzed the effects of Tat on cellular gene expression during various phases of the cell cycle.

Results

SOM and k-means clustering analyses revealed a dramatic alteration in transcriptional activity at the G1/S checkpoint. Tat regulates the expression of a variety of gene ontologies, including DNA-binding proteins, receptors, and membrane proteins. Using siRNA to knock down expression of several gene targets, we show that an Oct1/2 binding protein, an HIV Rev binding protein, cyclin A, and PPGB, a cathepsin that binds NA, are important for viral replication following induction from latency andde novoinfection of PBMCs.

Conclusion

Based on exhaustive and stringent data analysis, we have compiled a list of gene products that may serve as potential therapeutic targets for the inhibition of HIV-1 replication. Several genes have been established as important for HIV-1 infection and replication, including Pou2AF1 (OBF-1), complement factor H related 3, CD4 receptor, ICAM-1, NA, and cyclin A1. There were also several genes whose role in relation to HIV-1 infection have not been established and may also be novel and efficacious therapeutic targets and thus necessitate further study. Importantly, targeting certain cellular protein kinases, receptors, membrane proteins, and/or cytokines/chemokines may result in adverse effects. If there is the presence of two or more proteins with similar functions, where only one protein is critical for HIV-1 transcription, and thus, targeted, we may decrease the chance of developing treatments with negative side effects.
Increased serum HO-1 in hemophagocytic syndrome and adult-onset Still's disease: use in the differential diagnosis of hyperferritinemia
Authors: Kirino Yohei , Takeno Mitsuhiro , Iwasaki Mika , Ueda Atsuhisa , Ohno Shigeru , Shirai Akira , Kanamori Heiwa , Tanaka Katsuaki , Ishigatsubo Yoshiaki
Published: March 2005

Heme oxygenase-1 (HO-1), an inducible heme-degrading enzyme, is expressed by macrophages and endothelial cells in response to various stresses. Because ferritin synthesis is stimulated by Fe2+, which is a product of heme degradation, we examined the relation between HO-1 and ferritin levels in the serum of patients with hemophagocytic syndrome (HPS), adult-onset Still's disease (ASD), and other diseases that may cause hyperferritinemia. Seven patients with HPS, 10 with ASD, 73 with other rheumatic diseases, 20 with liver diseases, 10 recipients of repeated blood transfusion because of hematological disorders, and 22 healthy volunteers were enrolled. Serum HO-1 and ferritin levels were determined by ELISA. Expression of HO-1 mRNA and protein by peripheral blood mononuclear cells (PBMCs) was determined by real-time PCR and immunocytochemical techniques, respectively. Serum levels of HO-1 were significantly higher in patients with active HPS and ASD than in the other groups (P < 0.01). HO-1 levels were not elevated in patients with other causes of hyperferritinemia but were moderately elevated in patients with dermatomyositis/polymyositis. Among patients with HPS and ASD, serum HO-1 levels correlated closely with serum ferritin levels, and the levels of both returned to normal after therapy had induced remission. Increased expression of HO-1 mRNA was confirmed in PBMCs from some patients with HPS and ASD. Hyperferritinemia correlated closely with increased serum HO-1 in patients with HPS and ASD but not other conditions, indicating that measurement of serum HO-1 and ferritin levels would be useful in the differential diagnosis of hyperferritinemia and perhaps also in monitoring disease activity in HPS and ASD.
CD134 as target for specific drug delivery to auto-aggressive CD4+T cells in adjuvant arthritis
Authors: Boot Elmieke PJ , Koning Gerben A , Storm Gert , Wagenaar-Hilbers Josée PA , van Eden Willem , Everse Linda A , Wauben Marca HM
Published: March 2005

T cells have an important role during the development of autoimmune diseases. In adjuvant arthritis, a model for rheumatoid arthritis, we found that the percentage of CD4+ T cells expressing the activation marker CD134 (OX40 antigen) was elevated before disease onset. Moreover, these CD134+ T cells showed a specific proliferative response to the disease-associated epitope of mycobacterial heat shock protein 60, indicating that this subset contains auto-aggressive T cells. We studied the usefulness of CD134 as a molecular target for immune intervention in arthritis by using liposomes coated with a CD134-directed monoclonal antibody as a drug targeting system. Injection of anti-CD134 liposomes subcutaneously in the hind paws of pre-arthritic rats resulted in targeting of the majority of CD4+CD134+ T cells in the popliteal lymph nodes. Furthermore, we showed that anti-CD134 liposomes bound to activated T cells were not internalized. However, drug delivery by these liposomes could be established by loading anti-CD134 liposomes with the dipalmitate-derivatized cytostatic agent 5'-fluorodeoxyuridine. These liposomes specifically inhibited the proliferation of activated CD134+ T cells in vitro, and treatment with anti-CD134 liposomes containing 5'-fluorodeoxyuridine resulted in the amelioration of adjuvant arthritis. Thus, CD134 can be used as a marker for auto-aggressive CD4+ T cells early in arthritis, and specific liposomal targeting of drugs to these cells via CD134 can be employed to downregulate disease development.
Complete Response to Neoadjuvant Chemoradiotherapy in Esophageal Carcinoma Is Associated With Significantly Improved Survival
Authors: Berger Adam C. , Farma Jeffrey , Scott Walter J. , Freedman Gary , Weiner Louis , Cheng Jonathan D. , Wang Hao , Goldberg Melvyn
Published: March 2005

Purpose

Attempts to improve survival of patients with esophageal cancer have been made using induction chemoradiotherapy (CRT) followed by surgery. A large single-center experience was reviewed to determine which treatment-related variables could predict survival and recurrence.

Patients and Methods

All patients undergoing esophagectomy between January 1994 and December 2002 were reviewed. Univariate and multivariate analyses were performed using log-rank and Cox proportional hazards models, and survival curves were estimated using the Kaplan-Meier method.

Results

Of 171 patients with invasive cancer, 131 (77%) underwent preoperative CRT. The average age was 60 years, and most patients were male (85%). Operations performed included Ivor-Lewis (60%), transhiatal (8%), three-hole (23%), or left thoracoabdominal (8%) esophagectomy. Perioperative mortality rate was 5%. Median overall survival (OS) of the entire group was 33 months, and the 5-year OS rate was 26%. Induction CRT was associated with a 33% 5-year survival rate compared with 11% for surgery alone (P = .43). Patients downstaged to pathologic stage 0 or I had an improved OS and disease-free survival (DFS) compared with those patients who were not downstaged (P = .022). Additionally, the ability to perform an R0 resection was a significant factor for OS and DFS (n = 130; P < .0001 and P <.0002, respectively).

Conclusion

Response to CRT and the ability to perform an R0 resection are associated with significantly improved survival in patients with esophageal carcinoma.
Survival After Recurrence of Ewing’s Sarcoma Family of Tumors
Authors: Barker Lisa M. , Pendergrass Thomas W. , Sanders Jean E. , Hawkins Douglas S.
Published: March 2005

Purpose

The overall survival (OS) of patients with relapsed Ewing’s sarcoma family of tumors (ESFT) is poor, and the relative benefit of high-dose therapy (HDT) is controversial.

Patients and Methods

We retrospectively identified 55 consecutive ESFT patients with adequate medical records for review, who were treated at Children’s Hospital and Regional Medical Center and who developed disease recurrence between January 1, 1985 and December 31, 2002.

Results

The median relapse-free interval (RFI) from diagnosis to first recurrence was 17 months (range, 5 to 90 months). Most recurrences were metastatic only (39 patients) or local and metastatic (10 patients). Twenty-seven patients (49%) achieved a partial or complete response to second-line treatment, with a median duration of response of 27 months (range, 5 to 119+ months). The 5-year OS rate for all relapsed patients was 23% (95% CI, 11% to 35%). By univariate analysis, improved OS was associated with response to second-line treatment versus no response (46% v 0%, respectively; P < .0001), RFI ≥ 24 months versus less than 24 months (48% v 12%, respectively; P = .0001), and no metastases at initial diagnosis versus presence of metastases (31% v 12%, respectively; P = .05). Because all 13 patients who received HDT also had responsive relapse, we performed a multivariate analysis. Reduced risk of death was associated with response to second-line therapy (relative risk, 0.14; 95% CI, 0.05 to 0.40), RFI ≥ 24 months (relative risk, 0.29; 95% CI, 0.13 to 0.66), and receiving HDT (relative risk, 0.26; 95% CI, 0.08 to 0.85).

Conclusion

HDT as consolidation therapy for relapsed ESFT seems to be associated with improved OS, even after adjusting for RFI and response to second-line treatment.
Improved Detection of Prostate Cancer Using Classification and Regression Tree Analysis
Authors: Garzotto Mark , Beer Tomasz M. , Hudson R. Guy , Peters Laura , Hsieh Yi-Ching , Barrera Eduardo , Klein Thomas , Mori Motomi
Published: March 2005

Purpose

To build a decision tree for patients suspected of having prostate cancer using classification and regression tree (CART) analysis.

Patients and Methods

Data were uniformly collected on 1,433 referred men with a serum prostate-specific antigen (PSA) levels of ≤ 10 ng/mL who underwent a prostate biopsy. Factors analyzed included demographic, laboratory, and ultrasound data (ie, hypoechoic lesions and PSA density [PSAD]). Twenty percent of the data was randomly selected and reserved for study validation. CART analysis was performed in two steps, initially using PSA and digital rectal examination (DRE) alone and subsequently using the remaining variables.

Results

CART analysis selected a PSA cutoff of more than 1.55 ng/mL for further work-up, regardless of DRE findings. CART then selected the following subgroups at risk for a positive biopsy: (1) PSAD more than 0.165 ng/mL/cc; (2) PSAD ≤ 0.165 ng/mL/cc and a hypoechoic lesion; (3) PSAD ≤ 0.165 ng/mL/cc, no hypoechoic lesions, age older than 55.5 years, and prostate volume ≤ 44.0 cc; and (4) PSAD ≤ 0.165 ng/mL/cc, no hypoechoic lesions, age older than 55.5 years, and 50.25 cc less than prostate volume ≤ 80.8 cc. In the validation data set, specificity and sensitivity were 31.3% and 96.6%, respectively. Cancers that were missed by the CART were Gleason score 6 or less in 93.4% of cases. Receiver operator characteristic curve analysis showed that CART and logistic regression models had similar accuracy (area under the curve = 0.74 v 0.72, respectively).

Conclusion

Application of CART analysis to the prostate biopsy decision results in a significant reduction in unnecessary biopsies while retaining a high degree of sensitivity when compared with the standard of performing a biopsy of all patients with an abnormal PSA or DRE.