bluuebunny/crossref_metadata_2025 huggingface dataset:
Undergraduate training in palliative medicine in Germany: what effect does a curriculum without compulsory palliative care have on medical students’ knowledge, skills and attitudes?
Authors: Ostgathe Christoph , Voltz Raymond , Nauck Friedemann , Klaschik Eberhard
Published: March 2007

Introduction: The effect of a curriculum without compulsory courses in palliative medicine on students’ knowledge, kills and attitudes towards the care of dying patients and decisions at the end of life was investigated.

Methods: In a cross sectional, questionnaire based survey at the medical school of Bonn 1st, 3rd and 5th year students had to grade their knowledge and skills in items concerning palliative medicine. Attitudes towards end of life decisions were queried.

Results: The return rate was 78%. Significant increase in self estimation of certainty comparing 1st to 5th year students were detected for the items distinction between palliative and curative medicine (p <0.001), symptom control (p <0.001), pain management (p =0.001) and communication (p =0.036). No significant differences were recorded for the items accompaniment of dying patients, breaking bad news and integration of spiritual aspects. The low overall certainty is reflected in poor knowledge. A significant decrease of the approval for euthanasia by request was evident (p =0.012).

Discussion: A medical curriculum without compulsory course does increase confidence in some of the core competencies in palliative care, but the overall results at the end of the training are poor. The WHO claims that palliative care has to be “compulsory in courses leading to a basic professional qualification” has still to be fulfilled in Germany. This study can serve as a baseline to evaluate the effect of mandatory courses in palliative care.
Loss and change: experiences of people severely affected by multiple sclerosis
Authors: Edmonds Polly , Vivat Bella , Burman Rachel , Silber Eli , Higginson Irene J
Published: March 2007

This study aimed to explore important issues for people severely affected by multiple sclerosis (MS). Individual interviews were conducted with 23 people with MS (PwMS) and 17 informal carers, the data relating to 32 PwMS. Information was obtained about 19 females and 13 males, with a mean age of 55, median time from diagnosis was 14.5 years, and physical disabilities ranged from mild to severe, although fifteen patients had severe disabilities. Twenty-six of the 32 individuals were unable to walk, 24 were catheterised, and 18 had considerably impaired or no upper limb function. Personal issues in relation to loss and change, particularly in terms of losses of or changes in physical abilities, including maintaining mobility, independence, relationships and social role were raised commonly in response to an open-ended question about what issues were important in living with MS. Coping with MS requires individuals to deal with the losses and changes brought about by their illness. Our study suggests that even patients who have had MS for many years and are now severely affected continue to experience loss and change. We recommend that attention be given to emotional support which specifically addresses three main areas of dealing with loss and change for people that are severely affected - physical issues, independence and relationships. Palliative care providers may have expertise in managing loss that could be useful for these patients in partnership with neurological services.
Feeling like a burden to others: a systematic review focusing on the end of life
Authors: McPherson Christine J , Wilson Keith G , Murray Mary Ann
Published: March 2007

Research into the burden of illness has focused predominantly on family caregivers, with little consideration of the other side of the caregiving relationship-care recipients’ perspectives on having become a ‘burden to others’. However, there is now a small but growing body of evidence to suggest that worry about creating burden to others is a common and troubling concern for people who are nearing the end of their lives. This concern is referred to as ‘self-perceived burden’. The present study provides a systematic review of the literature, addressing self-perceived burden at the end of life. Using standard methods, literature was searched for relevant studies in palliative care and related fields. The review revealed that self-perceived burden is reported as a significant problem by 19- 65% of terminally ill patients. It is correlated with loss of dignity, suffering, and a ‘bad death’. Self-perceived burden has also been identified as a relevant factor in death-hastening acts among patients with life-threatening illness, as well as in clinical decisions, such as the choice of place of care at the end of life, advance directives, and acceptance of treatment. Given the unique challenges faced by patients with advanced disease and their families, there is a need for further investigation into this under-researched area.
A Response to Tony Richie’s ‘Azusa Era Optimism: Bishop J.H. King’s Pentecostal Theology of Religions as a Possible Paradigm for Today’
Authors: Kärkkäinen Veli-Matti
Published: March 2007

In this appreciative response to Tony Richie’s paper, Richie is urged to relate the Pentecostal theology of religions of Bishop King to a wider theology of religions discourse and to be more specific about what he means by King’s alleged ‘optimism’ about religions.
Pneumatological Perspectives for A Theology of Nature: The Holy Spirit in Relation to Ecology and Technology
Authors: Gabriel Andrew
Published: March 2007

How does the relationship of the Holy Spirit to creation guide theology of nature? This paper will propose that, on a cosmological level, the Spirit, as the ‘Giver of Life’, produces kinship among creatures, that the Spirit suffers with creation’s suffering and as his perfecting work is frustrated, and that the Spirit gifts certain aspects of technological culture. The presence of the Spirit in nature causes us to respect nature, nevertheless, the Spirit may guide people to shape nature in ways that are consonant with the Spirit’s life-giving work.
Pentecostal Ecclesiology: A Methodological Proposal for A Diverse Movement
Authors: Clifton Shane
Published: March 2007

This paper is stimulated by the need to develop an ecclesiological method that is capable of describing and analysing the diverse self-understandings that characterize global Pentecostalism (or any Christian Church). It begins by observing the limitations of idealist approaches to ecclesiology, and instead proposes a concrete ecclesiological method. Concrete ecclesiology will include the narrative of particular Churches and movements, describe the explicit and implicit self-understanding that accompanies this narrative, and assess ecclesial transitions. Since the Church is a human and divine community, analysis will incorporate theological categories and the human sciences. Consequently, the paper considers how the ecclesiologist might appropriate the multifaceted discipline of sociology. The goal is an ecclesiology that is not reduced only to ideal categories, but that is capable of analysing the complex reality of indigenous Pentecostal Churches.
Enhancing Knowledge Management in Design Education Through Systematic Reflection Practice
Authors: Agouridas Vassilis , Race Phil
Published: March 2007

The significant role of reflection in sustaining the quality of learning and teaching (L&T) activities at high levels has been widely acknowledged in literature. Reflection has been identified as a key factor underpinning both successful learning by students and successful continuing professional development by their teaching staff in higher education. This study focuses on aspects associated with the individual reflection practice of teaching staff. It is proposed and maintained that the establishment of systematic reflection practice has a central role in enhancing knowledge management in design education. To this end, the consistency and coherence, in which key perspectives of reflection are considered and evidenced by teaching staff, need to be both ensured and sustained. Reflection Space is introduced as an approach to support the establishment of systematic1, evidenced2, and traceable reflection practice. It is a means of representing the nature, or perspectives, of reflection required on L&T and it has been applied and evaluated to a number of L&T contexts. An application of Reflection Space is demonstrated through a case study that dealt with the development of a Design Studio module delivered to Year 2 Product Design students. Evaluation of the application has shown that use of Reflection Space during the reflection phase of L&T activities can ensure that key reflective perspectives of L&T have been considered and evidenced. As a result, actions for the enhancement and/or improvement of the deployed L&T activities can be determined in a systematic, evidenced, and traceable manner.
A Flexible and Robust Approach for Preliminary Engineering Design Based on Designer's Preference
Authors: Nahm Yoon-Eui , Ishikawa Haruo , Yang Young-Soon
Published: March 2007

This study proposes a new set-based design approach for preliminary engineering design that intrinsically contains various sources of uncertainties. The goal is to achieve design flexibility and robustness while capturing designer's preference. The proposed design approach includes three computational methods: (1) set representation method to specify the varying degree of desirability of a ranged set of design solutions and performance requirements, thereby enabling the manipulation of uncertain design solutions and requirements based on designer's preference structure; (2) set propagation method to obtain performance possibilities achievable by uncertain design solutions, thus exploring a broader design possibilities; (3) set narrowing method to generate a ranged set of feasible solutions (i.e., robust and flexible solution set) instead of single point solution that satisfies changing sets of performance requirements by eliminating infeasible and inferior subsets of solutions, thus allowing designs to be readily adapted to changing conditions. Finally, the proposed design approach is illustrated with a successful implementation of real industrial design problem (i.e., vehicle side-door structure design) in the simulation-based design environment.
The bioethics of medical research in very poor countries
Authors: Tausig Mark , Subedi Sree , Subedi Janardan
Published: March 2007

Sociologists have had only a marginal effect on the development of bioethical principles for medical research despite their interest in the effects of social and economic inequality on health and its implications for issues of social and individual justice. In this article we review existing bioethical standards for conducting medical research in very poor countries. Given the substantial differences in individual exposure to health risks and the availability of health protective resources as well as differences in the disease burden and mortality and morbidity at the population level, it is clear that illness in poor countries can be better understood using a social causation of illness perspective. In turn we suggest that such a perspective can be useful for identifying bioethical standards that better apply in this context.
Maintaining face in the presentation of depression: constraining the therapeutic potential of the consultation
Authors: Pollock Kristian
Published: March 2007

This article discusses the concerns of patients diagnosed with depression to preserve ‘face’ in social and medical encounters. The findings are from a qualitative study of patient and GP accounts of the presentation, recognition and treatment of depression. Medical consultations are difficult encounters to accomplish successfully, especially for patients, who often strive to protect their privacy and personal integrity through the maintenance of face. Face work reveals the concern of participants to contribute to the success of the consultation as a social interaction. Patients' strategy of maintaining face helps to account for the commonly reported underdetection of psychosocial distress in general practice consultations. Many people do not regard the experience of psychosocial distress as an appropriate topic for medical consultation or scrutiny. In this case, face work can function as a means of maintaining privacy and resisting medical diagnosis and intervention. The concept of face has relevance in other areas of clinical care, including chronic and enduring pain, functional disorders, medically unexplained symptoms and even terminal illness. Consideration of face work reveals the extent to which the pressure to contribute to the success of the consultation as a social encounter may constrain participants' capacity to realize its therapeutic potential. The extent to which clinical interactions are governed by social etiquette also helps to explain the continuing inertia of the formal health care system and the difficulty of changing the ways that patients and doctors communicate with each other, and of increasing patients' involvement in medical consultations.
Does money buy better health? Unpacking the income to health association after midlife
Authors: Berry Brent
Published: March 2007

This article estimates the effect of household financial resources on health after midlife using models that minimize health-related selectivity and unobserved heterogeneity bias. I focus on the self-rated health and mobility limitations of adults transitioning into retirement over six panels of the Health and Retirement Study (1992–2002; age 51–61 at wave one; N = 7602). Standard regression models that adjust for health-related selection with prospective and retrospective controls suggest a significant influence of long-term income on health, but an insignificant influence of short-term income. Further adjustment for unobserved fixed effects also suggests that short-term income is insignificant. Sizable recent and long-term health feedbacks to income for a portion of the HRS respondents underscore the need to control for the confounding influence of health over the lifecourse. Together these results suggest that adults after midlife are heterogeneous with respect to the causal and selective processes generating the observed association between income and health.
lIlness as argumentation: a prolegomenon to the rhetorical study of contestable complaints
Authors: Segal Judy Z.
Published: March 2007

The resources of rhetorical theory, the classical theory of persuasion, can be marshaled to help physicians evaluate patient complaints for which there is no corresponding objective evidence and which rely, therefore, on the persuasiveness of patients to be taken seriously (contestable complaints). An appropriate focus for the evaluation of such complaints is argumentation itself: what, in the absence of objective evidence of disease, counts as a good argument for a patient to be eligible for medical attention? How do patients convince physicians that they are ill and in need of care – and, conversely, how do physicians convince patients, when the need arises, that they are well and not good candidates for medical intervention? Two rhetorical concepts are especially productive for the analysis of argumentation. One is kairos, the Sophistic notion of contingency, and the other is pisteis, the Aristotelian catalogue of persuasive appeals. A focus on types of arguments directs attention away from types of patients (difficult, suspect, malingering and so on), and provides a more neutral means of judging claims to illness.
Analysing sky luminance scans and predicting frequent sky patterns in Singapore
Authors: Wittkopf S K , Soon L K
Published: March 2007

A thorough analysis of sky distributions can help in the prediction of daylight patterns and thus provides a good understanding of architectural window and building envelope design. This paper introduces three methods of analysis for sky distributions, namely the relative indicatrix and gradation classification, and two other independent methods established by Kittler and Tregenza. All these three methods were verified for their feasibility for analysing the extreme daylight conditions in Singapore, which is located at the equator. The most suitable approach, from Tregenza, was eventually adopted in analysing the measured data from Singapore IDMP station. The prediction of frequent sky patterns in Singapore was based on the CIE Standard General Skies, as well as a complete version considering all 36 theoretical sky types.
Predicting daylight availability dynamically based on forecasts of a weather observatory
Authors: Ng E , Gadi A , Wong F , Mu J , Gadi A , Lee M
Published: March 2007

By using measured data of the research class IDMP station, a subset of three sky types and their probability of occurrence has previously been established to represent sky conditions of Hong Kong. This was dubbed the Hong Kong Representative Sky (HKRS). The HKRS allows a better prediction of daylight on the vertical surfaces of buildings than the CIE Overcast Sky. The HKRS was still a static representation. This paper investigates the possibility of using the weather predictions of the observatory to establish dynamically the HKRS. A methodology is proposed, and the results indicate that the approach is feasible. It is established that the weather prediction information issued by the Hong Kong Observatory (HKO) provides a reliable means for estimating probabilities of the sky types at a particular moment. By using this information, a better prediction of vertical sky component (VSC) on building surfaces, with a reduction of 20–30% mean absolute error, can be achieved. Engineers and architects may use this more accurate information to design more dynamically.
Lighting for people with dementia
Authors: Torrington J M , Tregenza P R
Published: March 2007

Guidelines for the design of lighting in residential buildings used by people with dementia are derived from the results of two research projects and a literature review. General guidance on lighting for the older person is summarised and the special requirements of those living with dementia are examined under four headings: the diurnal cycle, a view of nature and the outside world, support for individual and social activities, and recognition of place.

The aim is a visual environment that enhances physical well-being and enjoyment of life.
Equatorial sunpath diagrams for sunlight reflected from specular surfaces
Authors: Lynes J A
Published: March 2007

A flat reflective plane may be represented by a radial straight line on an equatorial sunpath diagram. Sunpath images are mirrored across this radial line. Analysis of reflected sunpaths is illustrated on an equatorial stereographic diagram. A gnomonic alternative is discussed.
Re-presenting war
Authors: Chapman James
Published: March 2007

This article examines a cycle of British drama-documentaries about the Second World War broadcast in 2004-5: Dunkirk, D-Day, When Hitler Invaded Britain D-Day to Berlin and Blitz: London's Firestorm. It places these films in the context of the drama-documentary tradition in British film and television; it considers the institutional and cultural contexts of their production; it analyses their formal properties, especially their combination of actuality film with dramatic reconstruction; and it examines the extent to which they offer a revisionist perspective on the British historical experience of the Second World War. The article argues that these films represent a significant new direction for representing history on television.
Docudramatizing history on TV
Authors: Ebbrecht Tobias
Published: March 2007

The 60th anniversary celebration of the end of the Second World War became an important political, social and media event. Memory rituals, speeches and official announcements, celebrations, movies and reports created an ensemble of social activities that re-dramatized the historic event. In these kinds of memorial rituals the re-dramatization of history becomes part of collective memory, in which a shared image of historic incidents is created. Media and especially television play an important role in this making of history. Today, television is one of the most important agents for communicating historical events. At the same time the tendency of historical television documentary is to adopt increasingly popular forms and elements of feature films. This has led to a popular form of historical event television. One of its main genres is the docudrama. The article reviews contemporary docudramas about Nazism and Second World War on German television.
A small screen alternative to stone and bronze
Authors: Hanna Emma
Published: March 2007

This article examines the first major British television series about the First World War, The Great War (BBC, 1964), in terms of its cultural, historical and aesthetic significance. As a central component of the BBC`s 50th anniversary commemorative programme to mark the outbreak of war, the series was a major media event -a small-screen memorial cast in sounds and images instead of stone and bronze. This article looks at how the British television audience responded to this form of on-screen commemoration. Material for this article was derived from the series' extensive production records housed in the BBC Written Archives Centre at Caversham, Berkshire. This was supplemented by, among other sources, material from interviews and correspondence with several surviving members of the production team. This allows a broader understanding of the motivations of those involved in the production of a groundbreaking historical series, while acknowledging the wide-ranging nature of its audience.
History on television
Authors: Bell Erin , Gray Ann
Published: March 2007

What appears on screen as `TV history' is limited by a number of possible factors; technological, financial and cultural. This article considers some of these limitations, as little is known about the processes whereby representations of the past are mediated, shaped and transformed through television. This raises pertinent questions about the construction, distribution and marketing of narratives about national and other pasts. Using oral history techniques in the research, this article seeks insights from historians involved in history programming; from this rich seam of information it focuses on two themes: the respondents' own representation on camera as historians, and their views on the style and modes of address of TV presenter-historians. This is analysed with reference to notions of charismatic television personalities and dominant narrative structures, drawing on, among others, Hayden White. It is suggested that these modes of address and televisual forms offer the viewer particular relationships to knowledge and ways of knowing.
Gangster in guerilla face
Authors: Zilberg Elana
Published: March 2007

Doble cara (double/two-faced) is a key trope in Salvadoran political folklore. It is a folk theory of mimesis, which attempts to `master the absent presence of the other' through a discourse of conspiracy. The term has a history in the US-funded Salvadoran civil war. In this article, I consider how doble cara has come to be deployed around a new and pivotal social subject — Salvadoran immigrant gang youth deported from the USA — and how these deported youth emerge as a packed and displaced sign for the trauma of post-civil war violence, the failed promise of peace, and ongoing entanglements between the USA and El Salvador. The article is written in conversation with Begoña Aretxaga, who inspired many of the questions explored here.
Snow White in different guises: Interlingual and intercultural exchanges between grandparents and young children at home in East London
Authors: Gregory Eve , Arju Tahera , Jessel John , Kenner Charmian , Ruby Mahera
Published: March 2007

Grandparents play a significant role in childcare and one activity that frequently occurs within this context is story-reading. However, relatively little attention has been given to the potential part that grandparents can play in terms of language and literacy development of young children.This article reports on work investigating the interlingual and intercultural exchanges occurring in a home setting in East London. In particular, it focuses on how the traditional heritage pattern of story and rhyme reading by a grandmother of Bengali origin is fused with practices experienced by her six-year old grandchild.The data reveal not only the multiple worlds inhabited by the grandchild during story-reading but also the syncretism of these worlds on a number of levels.This article contributes to the small but growing body of investigation into the reading styles occurring within families from different cultural backgrounds.
Mother—child story book interactions: Literacy orientation of pre-schoolers with hearing impairment
Authors: Kaderavek Joan N. , Pakulski Lori A.
Published: March 2007

The current study explored literacy interest or orientation of pre-school children with hearing impairment during mother—child story book interactions.Twelve pre-schoolers with varying types and levels of hearing impairment were observed during mother—child home book reading and toy play. Story books included both narrative and manipulative book genres. Child orientation to the task was qualitatively rated with a four-point Orientation Rating to Book Reading/Toy Play; mothers' modification of the book's text was scored with the Modification of the Book's Text Rating. Results indicated that (1) children should have more than one opportunity to explore and interact with a book before orientation is assessed, (2) children demonstrated a higher mean level of orientation to manipulative books versus narrative books across the three interactions, and (3) modification was negatively correlated with children's age (i.e. the text was more likely to be read verbatim with younger children).
Picturing economic childhoods: Agency, inevitability and social class in children's picture books
Authors: Saltmarsh Sue
Published: March 2007

This article considers ideological, pedagogical and constitutive functions of children's picture books, with particular emphasis on the ways in which texts construct children and childhood in economic terms. Through an analysis of Lauren Childs' Hubert Horatio Bartle Bobton-Trent and Anthony Browne's Voices in the Park, the article interrogates the ways in which these texts' depictions of individuals and families function to locate children and childhood as central to notions of individual, family and social economies. Drawing on insights from feminist poststructuralist research concerned with the textual production of gendered subjectivities, I consider how gendered notions of childhood agency and the inevitability of social class location are implicated in the production of subject positions that are defined by the navigation of socioeconomic circumstances. The argument is made that the subjective, relational, and social processes associated with picture book reading map onto and (re)produce discourses of children and childhood as explicitly economic categories.
The Diabetic Foot: Perspectives From Chennai, South India
Authors: Viswanathan Vijay
Published: March 2007

Foot ulcers are a significant complication of diabetes mellitus and often precede lower extremity amputation. The most frequent underlying etiologies are neuropathy, trauma, deformity, high plantar pressures, and peripheral arterial disease. Loss of protective sensation is the primary factor in foot ulceration in diabetics. Mechanical stresses resulting from joint deformity, limited joint mobility, and poor foot care/footwear are important in the causal pathway of both neuropathic and ischemic ulcers. It was shown that the recurrence of foot infection was common among Indian diabetic patients (52%). A lesser prevalence of peripheral vascular disease (13%) among Indians was noted when compared with those in Western countries (48%). Smoking increases the risk by reducing blood circulation in the legs and reducing sensation in the feet. Prompt and aggressive treatment of diabetic foot ulcers can often prevent exacerbation of the problem and eliminate the potential for amputation. The aim of the therapy should be early intervention to allow prompt healing of the lesion and prevent recurrence once it is healed. Multidisciplinary management programs that focus on prevention, education, regular foot examinations, aggressive intervention, and optimal use of therapeutic footwear have demonstrated significant reductions in the history of lower extremity amputations.
Reduced natural killer (NK) function associated with high-risk myelodysplastic syndrome (MDS) and reduced expression of activating NK receptors
Authors: Epling-Burnette Pearlie K. , Bai Fanqi , Painter Jeffrey S. , Rollison Dana E. , Salih Helmut R. , Krusch Matthias , Zou JianXiang , Ku Edna , Zhong Bin , Boulware David , Moscinski Lynn , Wei Sheng , Djeu Julie Y. , List Alan F.
Published: March 2007

Myelodysplastic syndromes (MDS) are characterized by ineffective hematopoiesis with potential for progression to acute myeloid leukemia (AML). We compared natural killer (NK) cytolytic function in 48 MDS patients with 37 healthy donors and found reduced activity in the patient population (K562 cytolysis, 19% ± 21% SD versus 40% ± 17%) (P < .001). NK cytotoxicity in MDS patients was reduced against 3 disparate tumor targets with differential activating receptor requirement, suggesting global defects in NK function. Reduced NK function in MDS was significantly associated with higher International Prognostic Score (P = .01), abnormal karyotype (P = .05), the presence of excess blasts (P = .01), and age-adjusted bone marrow hypercellularity (P = .04). MDS patients had a display of the activating receptor NKp30, and NKG2D down-regulation closely correlated with impaired NK function (P = .001). NKG2D ligands (MICA and MICB) were expressed on CD34+ cells from bone marrow of 30% of MDS patients and a leukemic cell line derived from an MDS patient (MDS1). Collectively, these findings suggest that impairment of NK cytolytic function derives in part from reduced activating NK receptors such as NKG2D in association with disease progression. Evasion of NK immunosurveillance may have importance for MDS disease progression.
Long-term disease-free survivors with cytogenetically normal acute myeloid leukemia and MLL partial tandem duplication: a Cancer and Leukemia Group B study
Authors: Whitman Susan P. , Ruppert Amy S. , Marcucci Guido , Mrózek Krzysztof , Paschka Peter , Langer Christian , Baldus Claudia D. , Wen Jing , Vukosavljevic Tamara , Powell Bayard L. , Carroll Andrew J. , Kolitz Jonathan E. , Larson Richard A. , Caligiuri Michael A. , Bloomfield Clara D.
Published: March 2007

The clinical impact of MLL partial tandem duplication (MLL-PTD) was evaluated in 238 adults aged 18 to 59 years with cytogenetically normal (CN) de novo acute myeloid leukemia (AML) who were treated intensively on similar Cancer and Leukemia Group B protocols 9621 and 19808. Twenty-four (10.1%) patients harbored an MLL-PTD. Of those, 92% achieved complete remission (CR) compared with 83% of patients without MLL-PTD (P = .39). Neither overall survival nor disease-free survival significantly differed between the 2 groups (P = .67 and P = .55, respectively). Thirteen MLL-PTD+ patients relapsed within 1.4 years of achieving CR. MLL-PTD+ patients who relapsed more often had other adverse CN-AML–associated molecular markers. In contrast with previously reported studies, 9 (41%) MLL-PTD+ patients continue in long-term first remission (CR1; range, 2.5-7.7 years). Intensive consolidation therapy that included autologous peripheral stem-cell transplantation during CR1 may have contributed to the better outcome of this historically poor-prognosis group of CN-AML patients with MLL-PTD.
Postremission treatment of elderly patients with acute myeloid leukemia in first complete remission after intensive induction chemotherapy:results of the multicenter randomized Acute Leukemia French Association (ALFA) 9803 trial
Authors: Gardin Claude , Turlure Pascal , Fagot Thierry , Thomas Xavier , Terre Christine , Contentin Nathalie , Raffoux Emmanuel , de Botton Stephane , Pautas Cecile , Reman Oumedaly , Bourhis Jean-Henri , Fenaux Pierre , Castaigne Sylvie , Michallet Mauricette , Preudhomme Claude , de Revel Thierry , Bordessoule Dominique , Dombret Herve
Published: March 2007

In elderly patients with acute myeloid leukemia (AML) treated intensively, no best postremission strategy has emerged yet. This clinical trial enrolled 416 patients with AML aged 65 years or older who were considered eligible for standard intensive chemotherapy, with a first randomization comparing idarubicin with daunorubicin for all treatment sequences. After induction, an ambulatory postremission strategy based on 6 consolidation cycles administered monthly in outpatients was randomly compared with an intensive strategy with a single intensive consolidation course similar to induction. Complete remission (CR) rate was 57% with 10% induction deaths, and estimated overall survival was 27% at 2 years and 12% at 4 years, without notable differences between anthracycline arms. Among the 236 patients who reached CR, 164 (69%) were randomized for the postremission comparison. In these patients, the multivariate odds ratio in favor of the ambulatory arm was 1.51 for disease-free survival (P =.05) and 1.59 for overall survival from CR (P =.04). Despite repeated courses of chemotherapy associated with a longer time under treatment, the ambulatory arm was associated with significantly shorter rehospitalization duration and lower red blood cell unit and platelet transfusion requirements than observed in the intensive arm. In conclusion, more prolonged ambulatory treatment should be preferred to intensive chemotherapy as postremission therapy in elderly patients with AML reaching CR after standard intensive remission induction.
Differential response of lymphatic, venous and arterial endothelial cells to angiopoietin-1 and angiopoietin-2
Authors: Nguyen Vicky PKH , Chen Stephen H , Trinh Jason , Kim Harold , Coomber Brenda L , Dumont Daniel J
Published: March 2007

Background

The lymphatic system complements the blood circulatory system in absorption and transport of nutrients, and in the maintenance of homeostasis. Angiopoietins 1 and 2 (Ang1 and Ang2) are regulators of both angiogenesis and lymphangiogenesis through the Tek/Tie-2 receptor tyrosine kinase. The response of endothelial cells to stimulation with either Ang1 or Ang2 is thought to be dependent upon the origin of the endothelial cells. In this study, we examined the effects of the angiopoietins on lymphatic, venous and arterial primary endothelial cells (bmLEC, bmVEC and bmAEC, respectively), which were isolated and cultured from bovine mesenteric vessels.

Results

BmLEC, bmVEC and bmAEC cell populations all express Tie-2 and were shown to express the appropriate cellular markers Prox-1, VEGFR3, and Neuropilin-1 that define the particular origin of each preparation. We showed that while bmLECs responded slightly more readily to angiopoietin-2 (Ang2) stimulation, bmVECs and bmAECs were more sensitive to Ang1 stimulation. Furthermore, exposure of bmLECs to Ang2 induced marginally higher levels of proliferation and survival than did exposure to Ang1. However, exposure to Ang1 resulted in higher levels of migration in bmLECs than did to Ang2.

Conclusion

Our results suggest that although both Ang1 and Ang2 can activate the Tie-2 receptor in bmLECs, Ang1 and Ang2 may have distinct roles in mesenteric lymphatic endothelial cells.
Quantitative evaluation and selection of reference genes in mouse oocytes and embryos cultured in vivo and in vitro
Authors: Mamo Solomon , Gal Arpad Baji , Bodo Szilard , Dinnyes Andras
Published: March 2007

Background

Real-time PCR is an efficient tool to measure transcripts and provide valuable quantitative information on gene expression of preimplantation stage embryos. Finding valid reference genes for normalization is essential to interpret the real-time PCR results accurately, and understand the biological dynamics during early development. The use of reference genes also known as housekeeping genes is the most widely applied approach. However, the different genes are not systematically compared, and as a result there is no uniformity between studies in selecting the reference gene. The goals of this study were to compare a wide selection of the most commonly used housekeeping genes in mouse oocytes and preimplantation stage embryos produced under different culture conditions, and select the best stable genes for normalization of gene expression data.

Results

Quantitative real time PCR method was used to evaluate 12 commonly used housekeeping genes (Actb, Gapdh, H2afz, Hprt, Ppia, Ubc, Eef1e1, Tubb4, Hist2h2aa1, Tbp, Bmp7, Polr2a) in multiple individual embryos representing six different developmental stages. The results were analysed, and stable genes were selected using the geNorm software. The expression pattern was almost similar despite differences in the culture system; however, the transcript levels were affected by culture conditions. The genes have showed various stabilities, and have been ranked accordingly.

Conclusion

Compared to earlier studies with similar objectives, we used a unique approach in analysing larger number of genes, comparing embryo samples derived in vivo or in vitro, analysing the expression in the early and late maternal to zygote transition periods separately, and using multiple individual embryos. Based on detailed quantification, pattern analyses and using the geNorm application, we found Ppia, H2afz and Hprt1 genes to be the most stable across the different stages and culture conditions, while Actb, the classical housekeeping gene, showed the least stability. We recommend the use of the geometric averages of those three genes for normalization in mouse preimplantation-stage gene expression studies.
The molecular signature of therapeutic mesenchymal stem cells exposes the architecture of the hematopoietic stem cell niche synapse
Authors: Pedemonte Enrico , Benvenuto Federica , Casazza Simona , Mancardi Gianluigi , Oksenberg Jorge R , Uccelli Antonio , Baranzini Sergio E
Published: March 2007

Background

The hematopoietic stem cells (HSCs) niche of the bone marrow is comprised of HSCs, osteoblasts, endothelial cells and a stromal component of non-hematopoietic multipotent cells of mesenchymal origin named "mesenchymal stem cells" (MSCs).

Results

Here we studied the global transcriptional profile of murine MSCs with immuno-therapeutic potential and compared it with that of 486 publicly available microarray datasets from 12 other mouse tissues or cell types. Principal component analysis and hierarchical clustering identified a unique pattern of gene expression capable of distinctively classifying MSCs from other tissues and cells. We then performed an analysis aimed to identify absolute and relative abundance of transcripts in all cell types. We found that the set of transcripts uniquely expressed by MSCs is enriched in transcription factors and components of the Wnt signaling pathway. The analysis of differentially expressed genes also identified a set of genes specifically involved in the HSC niche and is complemented by functional studies that confirm the findings. Interestingly, some of these genes play a role in the maintenance of HSCs in a quiescent state supporting their survival and preventing them from proliferating and differentiating. We also show that MSCs modulate T cell functions in vitro and, upon in vivo administration, ameliorate experimental autoimmune encephalomyelitis (EAE).

Conclusion

Altogether, these findings provide novel and important insights on the mechanisms of T cell function regulation by MSCs and help to cement the rationale for their application in the treatment of autoimmune diseases.
Automated array-CGH optimized for archival formalin-fixed, paraffin-embedded tumor material
Authors: Joosse Simon A , van Beers Erik H , Nederlof Petra M
Published: March 2007

Background

Array Comparative Genomic Hybridization (aCGH) is a rapidly evolving technology that still lacks complete standardization. Yet, it is of great importance to obtain robust and reproducible data to enable meaningful multiple hybridization comparisons. Special difficulties arise when aCGH is performed on archival formalin-fixed, paraffin-embedded (FFPE) tissue due to its variable DNA quality. Recently, we have developed an effective DNA quality test that predicts suitability of archival samples for BAC aCGH.

Methods

In this report, we first used DNA from a cancer cell-line (SKBR3) to optimize the aCGH protocol for automated hybridization, and subsequently optimized and validated the procedure for FFPE breast cancer samples. We aimed for highest throughput, accuracy, and reproducibility applicable to FFPE samples, which can also be important in future diagnostic use.

Results

Our protocol of automated array-CGH on archival FFPE ULS-labeled DNA showed very similar results compared with published data and our previous manual hybridization method.

Conclusion

This report combines automated aCGH on unamplified archival FFPE DNA using non-enzymatic ULS labeling, and describes an optimized protocol for this combination resulting in improved quality and reproducibility.
Is abdominal wall contraction important for normal voiding in the female rat?
Authors: Smith Phillip P , Smith Christopher P , Boone Timothy B , Somogyi George T
Published: March 2007

Background

Normal voiding behavior in urethane-anesthetized rats includes contraction of the abdominal wall striated muscle, similar to the visceromotor response (VMR) to noxious bladder distension. Normal rat voiding requires pulsatile release of urine from a pressurized bladder. The abdominal wall contraction accompanying urine flow may provide a necessary pressure increment for normal efficient pulsatile voiding. This study aimed to evaluate the occurrence and necessity of the voiding-associated abdominal wall activity in urethane-anesthetized female rats

Methods

A free-voiding model was designed to allow assessment of abdominal wall activity during voiding resulting from physiologic bladder filling, in the absence of bladder or urethral instrumentation. Physiologic diuresis was promoted by rapid intravascular hydration. Intercontraction interval (ICI), voided volumes and EMG activity of the rectus abdominis were quantified. The contribution of abdominal wall contraction to voiding was eliminated in a second group of rats by injecting botulinum-A (BTX, 5 U) into each rectus abdominis to induce local paralysis. Uroflow parameters were compared between intact free-voiding and BTX-prepared animals.

Results

Abdominal wall response is present in free voiding. BTX preparation eliminated the voiding-associated EMG activity. Average per-void volume decreased from 1.8 ml to 1.1 ml (p < 0.05), and reduced average flow from 0.17 ml/sec to 0.11 ml/sec (p < 0.05). Intercontraction interval (ICI) was not changed by BTX pretreatment.

Conclusion

The voiding-associated abdominal wall response is a necessary component of normal voiding in urethane anesthetized female rats. As the proximal urethra may be the origin of the afferent signaling which results in the abdominal wall response, the importance of the bladder pressure increment due to this response may be in maintaining a normal duration intermittent pulsatile high frequency oscillatory (IPHFO)/flow phase and thus efficient voiding. We propose the term Voiding-associated Abdominal Response (VAR) for the physiologic voiding-associated EMG/abdominal wall response, to distinguish it from the visceromotor response (VMR) to noxious bladder distension.
Structure and characterization of a novel chicken biotin-binding protein A (BBP-A)
Authors: Hytönen Vesa P , Määttä Juha AE , Niskanen Einari A , Huuskonen Juhani , Helttunen Kaisa J , Halling Katrin K , Nordlund Henri R , Rissanen Kari , Johnson Mark S , Salminen Tiina A , Kulomaa Markku S , Laitinen Olli H , Airenne Tomi T
Published: March 2007

Background

The chicken genome contains a BBP-A gene showing similar characteristics to avidin family genes. In a previous study we reported that the BBP-A gene may encode a biotin-binding protein due to the high sequence similarity with chicken avidin, especially at regions encoding residues known to be located at the ligand-binding site of avidin.

Results

Here, we expand the repertoire of known macromolecular biotin binders by reporting a novel biotin-binding protein A (BBP-A) from chicken. The BBP-A recombinant protein was expressed using two different expression systems and purified with affinity chromatography, biochemically characterized and two X-ray structures were solved – in complex with D-biotin (BTN) and in complex with D-biotin D-sulfoxide (BSO). The BBP-A protein binds free biotin with high, "streptavidin-like" affinity (Kd ~ 10-13 M), which is about 50 times lower than that of chicken avidin. Surprisingly, the affinity of BBP-A for BSO is even higher than the affinity for BTN. Furthermore, the solved structures of the BBP-A – BTN and BBP-A – BSO complexes, which share the fold with the members of the avidin and lipocalin protein families, are extremely similar to each other.

Conclusion

BBP-A is an avidin-like protein having a β-barrel fold and high affinity towards BTN. However, BBP-A differs from the other known members of the avidin protein family in thermal stability and immunological properties. BBP-A also has a unique ligand-binding property, the ability to bind BTN and BSO at comparable affinities. BBP-A may have use as a novel material in, e.g. modern bio(nano)technological applications.
Hedgehog pathway activity in the LADY prostate tumor model
Authors: Gipp Jerry , Gu Guangyu , Crylen Curtis , Kasper Susan , Bushman Wade
Published: March 2007

Background

Robust Hedgehog (Hh) signaling has been implicated as a common feature of human prostate cancer and an important stimulus of tumor growth. The role of Hh signaling has been studied in several xenograft tumor models, however, the role of Hh in tumor development in a transgenic prostate cancer model has never been examined.

Results

We analyzed expression of Hh pathway components and conserved Hh target genes along with progenitor cell markers and selected markers of epithelial differentiation during tumor development in the LADY transgenic mouse model. Tumor development was associated with a selective increase in Ihh expression. In contrast Shh expression was decreased. Expression of the Hh target Patched (Ptc) was significantly decreased while Gli1 expression was not significantly altered. A survey of other relevant genes revealed significant increases in expression of Notch-1 and Nestin together with decreased expression of HNF3a/FoxA1, NPDC-1 and probasin.

Conclusion

Our study shows no evidence for a generalized increase in Hh signaling during tumor development in the LADY mouse. It does reveal a selective increase in Ihh expression that is associated with increased expression of progenitor cell markers and decreased expression of terminal differentiation markers. These data suggest that Ihh expression may be a feature of a progenitor cell population that is involved in tumor development.