bluuebunny/crossref_metadata_2025 huggingface dataset:
Implementing an electronic records management system
Authors: Gregory Keith
Published: July 2005

Purpose

This article seeks to consider the practical implementation of an electronic records management system in the National Health Service Purchasing and Supply Agency, a UK government agency.

Design/methodology/approach

It examines the four main stages from specifying and selecting the system through to post‐implementation evaluation and identifies the lessons learned within the context of the specific organisation and its record‐keeping culture.

Findings

The implementation of an ERM system causes a massive cultural shift that can be made easier with the backing of senior management. However, the desired results can also be achieved with a strong team if senior management empowers the project but does not get personally involved.

Originality/value

This article will give insight to those organisations that are thinking of implementing an ERM system.
Corporate governance and management of information and records
Authors: Willis Anthony
Published: July 2005

Purpose

This article aims to look at the intersection between corporate governance and information and records management.

Design/methodology/approach

The information provided in this article is based on the author’s own experience and literature reviews.

Findings

It is necessary to check that whatever systems are in place are working, and keep working, as organisational structures and requirements and laws and other circumstances change.

Originality/value

This article will assist in understanding what corporate governance is, what it involves and what its purpose is. In addition, some of the issues which arise in turning the concept into reality are also, hopefully, clear.
Archivist: friend or foe?
Authors: Moss Michael
Published: July 2005

Purpose

This paper sets out to explore the relationship between archives and the management of records, which are increasingly the product of the audit society, informed by a neo‐liberal agenda.

Design/methodology/approach

The article is based on the author's views.

Findings

It argues that there is no relationship between the two activities, except of the records themselves.

Originality/value

This article will be of interest to those interested in the archiving of records and its management.
Power imbalanced relationships: cases from UK fresh food supply
Authors: Hingley Martin K.
Published: July 2005

Purpose

This study investigates the issue of power in business‐to‐business relationships and constitutes an appraisal of the theory relating to issues of supply chain relationships; in which the received view from the relationship marketing literature with its emphasis on trust, dyadic symmetry and mutuality is questioned. It is contended, alternatively that other types of relationships, for example, those based on selfishness are equally relevant; and that power imbalanced business relationships are just as important to the understanding of business exchange.

Design/methodology/approach

Specific reference is made to power relationships in vertical food supply channels in the UK, where the majority of control lies in the hands of large multiple retailers. The paper cites case material drawn from studies into the relationships between UK‐based fresh food supplier organisations and their principal customers, the leading UK food retailers.

Findings

Specific outcomes are determined with regard to issues of power, mutuality and the nature of power‐dependent relationships. Power play is omnipresent in exchange relationships and is not always seen in a negative light. Relationship‐building is perfectly possible in asymmetric relationships and weaker parties are tolerant of power imbalance.

Research limitations/implications

The study concludes that power should be a central consideration when concerned with business relationships and that imbalances in power are no specific barrier to parties entering into relationships or to their success.

Practical implications

Findings from chosen case studies are transferable to other vertical channel circumstances. Any future investigation should consider the expression and limits of power and the boundaries of tolerance to power imbalance.

Originality/value

Provides evidence of the nature of power‐dependent business relationships.
A new approach for understanding hindrances to collaborative practices in the logistics channel
Authors: Bonet Dominique , Paché Gilles
Published: July 2005

Purpose

The paper attempts to determine whether decision‐makers in the manufacturing and retailing industry really wish to implement cooperative logistical relationships in the long term.

Design/methodology/approach

In order to answer the question, the authors have resorted to studying decision‐makers' private speech and to trying to discover the real meaning of their declarations. An original content analysis technique is implemented, which makes identifying hindrances to collaborative practices in the logistics channel possible.

Findings

From the main results, it can be concluded that logistical relationships still tend to lead to vertical competition. This finding is surprising when confronted with the development of academic literature on the so‐called foreseeable evolution of food marketing channels.

Research limitations/implications

The research relies on a reduced sample of 17 managers of major French manufacturing and retailing firms. Moreover, the data are generated by face‐to‐face interviews, which may introduce a biased view linked to the willingness to give a positive image of the firm.

Originality/value

The main results underline that the generalization of collaborative practices in the logistics channel is not always present in the frame of mind of decision‐makers as it appears through their private speech. From this point of view, the research can help in conducting negotiations, as well as in training future decision‐makers in business schools.
How to integrate the specificities of some food departments into a retail store organization?
Authors: Chabaud Didier , Codron Jean‐Marie
Published: July 2005

Purpose

To understand the impact of product specificity on organizational practices of retailers at the store level.

Design/methodology/approach

An Aokian framework is used that enables one to discriminate between food products according to their informational properties, and to connect these properties with organizational choices of centralization/decentralization.

Findings

Emphasizes the existing tension between the dominant “assimilation” organization pattern and the “encapsulation” pattern which fits better in with some specific product departments.

Research limitations/implications

Proposals are confronted with empirical data coming from professional press and experts interviews. Further empirical research is needed to consolidate the findings.

Practical implications

The paper points out the need to differentiate the management of departments according to their product specificity.

Originality/value

The paper stresses the impact of product specificity on department organization. It can be useful for the design of organizational mechanisms: work organization, incentives and career paths.
Private labels for premium products – the example of organic food
Authors: Jonas Astrid , Roosen Jutta
Published: July 2005

Purpose

This paper inquires into the tendency of German food retailers to market organic products as private‐label (PL) products.

Design/methodology/approach

After a review of the literature, results of a survey of retailers and processors, are presented.

Findings

Interviewed processors of the 62.7 per cent produce organic PL. Retailers sell organic PLs, because they care about “food safety”, “retail as a brand” and “health”, hoping to reach new customers. Requests for entry fees, investment grants and equipment allowances are less important for processors of organic PLs than for those not producing PLs. However, PL producers have to meet other conditions imposed by retailers and feel slight more dependent on few customers.

Originality/value

The results present the first survey of the competitive relation between organic manufacturers and retailers in Germany.
Predicting technological disasters: mission impossible?
Authors: Chapman Judith
Published: July 2005

Purpose

This paper aims to argue that, contrary to popular thinking, technological disasters are potentially predictable, and therefore amenable to risk assessment and mitigation. What is lacking at present is a more comprehensive understanding of the hazards, embedded in complex socio‐technical systems, which lead to such disasters.

Design/methodology/approach

The paper discusses several factors that contribute to hazard formation and development, including the interaction of human and mechanical components, ambiguity, evolutionary changes, innovation and poor communication in organisational systems. Two case studies of recent disasters in Australia are presented to provide illustrations of the complexity in socio‐technical systems and the hazards and risks that they harbour.

Findings

The paper finds that to progress, we need two things: better conceptual models and frameworks that reveal complexity and make systems more transparent, and more satisfactory approaches to risk management.

Originality/value

The paper concludes with some suggestions as to how the risks might be better understood and managed proactively.
Disaster management strategy for avoiding landslide induced losses to the villages in the vicinity of the Himalayan township of Mussoorie in Uttaranchal (India)
Authors: Uniyal Aniruddha , Rautela Piyoosh
Published: July 2005

Purpose

Many villages in the vicinity of the hill township of Mussorie in the Indian Himalayas are witnessing signs of an impending disaster. These villages are witnessing active wastage that might take an heavy toll of human interest during the monsoon season and therefore the paper proposes examining this subject.

Design/methodology/approach

A detailed study was undertaken in the area of Mussorie.

Findings

It is suggested that a series of prevention and mitigation measures (both structural and non‐structural) with the involvement of the local community are required for ruling out the possibility of any mishap in the area.

Originality/value

This paper highlights the importance of having a disaster management strategies for the region and involving the community with these.
Implications of ignoring the old disaster management plans
Authors: Rautela Piyoosh , Pande R.K.
Published: July 2005

Purpose

The paper aims to discuss the causes of the landslide event at Amparav in Kumaun Himalaya (Nainital district of Uttaranchal in India) and attempts to bring forth the importance of mass awareness regarding the past disaster events in their surroundings.

Design/methodology/approach

On the aftermath of the landslide tragedy of 23 September, 2004 field investigations were carried out to probe the causes and lapses that resulted in tragedy at a place where a detailed mitigation plan had been implemented.

Findings

The investigations reveal that a detailed landslide management strategy was prepared and implemented to protect this zone almost a century ago, with a thorough understanding of the mass wastage processes. Implementation of this plan safeguarded this zone for a long time, but the lack of awareness among the masses led to the violation of the very spirit of this plan. This culminated in the Amparav tragedy that took three human lives, besides the loss of a huge public and private infrastructure.

Research limitations/implications

The old study that led to the landslide management strategy could not be assessed and the article is based on information provided by the village elders.

Practical implications

The paper is an attempt to bring forth the finer details of the landslide management plan enacted in the region almost a century ago. It suggests the need for detailed surveys and planning in enacting any disaster management plan.

Originality/value

This paper would bring forth the importance of documenting the disaster management strategies of the region and sharing the significance of these with the masses so that they are deterred from even unintentionally violating the spirit of these plans.
ABITS: learning more about students through intelligent educational software
Authors: Mowlds Frances , Roche Bernard‐Joseph , Mangina Eleni
Published: July 2005

Purpose

One of the greatest challenges facing any intelligent tutoring system is being able to adapt its behaviour based on the student's current knowledge level, ability, needs and wishes within a course. This paper aims to present a framework of BDI agents within an agent‐based intelligent tutoring system (ABITS).

Design/methodology/approach

A conceptual discussion approach is taken.

Findings

The agents provide the core reasoning ability. In particular, the paper demonstrates how the system sources and refines a particular set of commonly available data. Also shows how these data are incorporated into the agents' belief set so that they may adapt their behaviour to support individual students.

Originality/value

Provides a framework that can improve learning procedures for future users of ABITS.
Differing student views of online learning modes across two programs in an Australian university
Authors: Dixon Kathryn , Pelliccione Lina , Dixon Robert
Published: July 2005

Purpose

Aims to investigate reactions to online delivery, student perceptions of the rates and depth of participation, and levels of engagement with the learning process in a Western Australian University.

Design/methodology/approach

The sample for this study comprised 108 students who were enrolled in both undergraduate and postgraduate programs. An interpretative method was adopted using a case study approach, with groups of internal and external students within one education department. This method was more appropriate than a more quantitative approach.

Findings

The results indicated that, while the students were technically competent overall, issues associated with equity and access varied between the groups and also between students enrolled in the same units. The sample had also re‐conceptualised the notion of “personal” which moved beyond simple physical proximity to enable the students to create their own community of learners.

Originality/value

Addresses the challenge for universities and instructional designers on how to increase the level and depth of interactivity in the online environment to further empower students to become independent learners.
The evaluation of a staff development (pilot) programme for online tutoring: a case study
Authors: Gerrard Catherine
Published: July 2005

Purpose

Aims to outline the issues and debates about a five‐week fully online staff development programme piloted in the University of Paisley, Scotland.

Design/methodology/approach

A case study was the approach taken.

Findings

The programme was designed to introduce lecturers to the theoretical and pedagogical issues surrounding online tutoring, while allowing them to get to grips with the delivery technology. The programme also provided academic staff with the opportunity to explore their attitudes towards using Computer‐Mediated Communications (CMC) in their teaching and to reflect on how they could utilise it to enhance their face‐to‐face teaching activities. Staff found the programme challenging but they also appreciated the opportunity to take part. Some reported feeling much more confident about using the technology.

Originality/value

Provides information on a programme designed to introduce face‐to‐face lecturers to the theoretical and pedagogical issues surrounding online tutoring while allowing them to become familiar with the technology.
Assumptions about participating in teacher education through the use of ICT
Authors: Olofsson Anders D. , Ola Lindberg J.
Published: July 2005

Purpose

With a philosophical stance in relation to education, this paper aims to discuss different understandings of participation in an information and communication technology (ICT)‐supported distance‐based teacher education program in Sweden.

Design/methodology/approach

The paper is based on early results from two studies, both of which involved a group of teacher‐trainees, with one interview and one questionnaire.

Findings

The findings indicate that there is a need to be explicit about the ontological assumptions inherent in the intended use of ICT. The conclusion is that the program in question is built on assumptions of realism and that ICT lays the ground for individual participation and works to tell the students apart.

Originality/value

Helps in understanding how ICT, and its use, can have different effects on different groups.
Asynchronous discussion forums in the changing landscape of the online learning environment
Authors: Lewinson Jennifer
Published: July 2005

Purpose

This report seeks to address the preliminary findings from a large‐scale study of the different ways in which the asynchronous discussion forum (ADF) is being used in the online learning environment.

Design/methodology/approach

A conceptual approach is taken.

Findings

The structural and functional variation of the ADF is depicted within a framework of institutional and instructional models. Epistemological distinctions are made with respect to the role of the instructor, student requirements, and the assessment of student learning.

Originality/value

The paper brings to light fundamental aspects of instructional quality and best practices involving the use of the ADF.
Bootstrapping methods applied for simulating laboratory works
Authors: Prodan Augustin , Campean Remus
Published: July 2005

Purpose

The aim of this work is to implement bootstrapping methods into software tools, based on Java.

Design/methodology/approach

This paper presents a category of software e‐tools aimed at simulating laboratory works and experiments.

Findings

Both students and teaching staff use traditional statistical methods to infer the truth from sample data gathered in laboratory experiments. However, the repeated laboratory experiments mean the consumption of a great deal of substances and reactants. At the same time, there are some ethically motivated reasons to reduce the number of animals used in experimentation. Using a bootstrapping tool and computer power, the experimenter can repeat the original experiment on computer, obtaining pseudo‐data as plausible as those obtained from the original experiment.

Originality/value

Provides data on implementing bootstrapping methods into software e‐tools, simulating laboratory experiments in didactic and research activities.
Examining effective and ineffective transformational project leadership
Authors: Strang Kenneth David
Published: July 2005

Purpose

Aims to examine effective and ineffective leader behaviors from direct participant observations in several cases of a large multiyear cross‐industry international research project to prove the hypothesis that effective team performance management requires strong transformational leadership.

Design/methodology/approach

Transformational and charismatic leadership theories are briefly discussed from management science to explain how their principles can apply to and be analyzed in the project domain and other fields. Several popular and proven group leader behavior measurement constructs are discussed to show how they can be applied for assessing group leader behavior in any field. Two flexible taxonomies are built for assisting in quantitatively and qualitatively explaining stakeholder perceptions of group leader behaviors and team performance. Four theoretically sampled case studies are analyzed. The taxonomies are analyzed quantitatively and the results are qualitatively evaluated.

Findings

The structured research illuminated that both effective and absent transformational leadership behaviors were practiced (idealized influence, inspirational motivation, individualized consideration, intellectual stimulation), which can go unnoticed and un‐reflected in the everyday pandemonium of busy project schedules, competing values, and organizational crises, yet in retrospect, these results show that passive or absent leadership is noticed by the team members and sponsors; moreover it negatively impacts on both project effectiveness and stakeholder satisfaction!

Research limitations/implications

Leaders, team members, stakeholders, and managers benefit from understanding transformational leadership, since it supports better human relations and organizational change. These cases show that effective team performance can result in minimal application of transformational leadership behaviors as long as they are not absent when required, and positive (not negative such as micro‐management).

Originality/value

This research suggests that leader behavior is complex since it is situational, supported by multiple and concurrent leadership and trait theories, as well as partly driven by dominant personality.
Information technology, human relations and knowledge work teams
Authors: Pyöriä Pasi
Published: July 2005

Purpose

The paper aims to serve as a reminder of the fact that informal organizational culture remains the foundation of healthy and productive work environments.

Design/methodology/approach

First, Elton Mayo's classic contribution to organization studies is brought to the reader's attention. Mayo was among the first scholars to assess empirically the importance of teamworking. Second, more recent studies are reviewed. The review highlights the value of collaborative problem solving among knowledge workers, i.e. experts whose job requires a high level of formal education, symbolic skills and the use of information technology (IT) in supporting their decision‐making process.

Findings

The review indicates that, contrary to an all‐too‐common belief, IT bears little direct relevance to knowledge workers' performance. However, if used properly, it can indirectly contribute to creating more space for interpersonal interaction by eliminating routine communication. In its essence, modern IT simply continues the long trend of the automation and mechanization of work.

Originality/value

The review suggests that existing knowledge about human behavior is far less than adequately applied. Therefore, the paper encourages managers to pay less attention to the latest technology and more attention to human relations.
Barnyard democracy in the workplace
Authors: Brotheridge Céleste M. , Keup Linda
Published: July 2005

Purpose

This paper aims to illustrate the interesting parallels that exist between the social behavior of farm animals and work‐teams as a means of offering a novel point of view from which to understand teams.

Design/methodology/approach

The empirical literature on the social behavior of farm animals is used as a starting‐point to identify the key factors that generate instability in social relationships and, as a result, demonstrate the existence of a dominance hierarchy. These factors are then analyzed in the context of the equivalent workplace literature in the areas of teamwork, bullying, and democracy.

Findings

There may be more of a connection between democracy in a barn and in a workplace than most people think. Both farm animals and humans have a tendency to form fairly stable social structures characterized by a dominance hierarchy in which there is: an established pecking order, differential access to resources; hazing of new members; penalties for non‐conformance; and a lack of personal space.

Practical implications

These factors contribute to instability in social relationships in the workplace and serve as potential explanations for the extent of aggression and incivility seen in today's organizations. Team leaders should pay attention to the markers of a dominance hierarchy and attempt to involve employees in democratic, participative work processes.

Originality/value

Team leaders will find this paper an unusual but effective way of considering how their teams are functioning.
Coaching, culture and leadership
Authors: Lloyd Bruce
Published: July 2005

Purpose

Philippe Rosinski, author of Coaching across Cultures (Nicholas Brealey, 2003) talks to Bruce Lloyd, Professor of Strategic Management, London South Bank University about the themes of coaching, culture and leadership.

Design/methodology/approach

Interview format.

Findings

The interview reveals the importance of purpose and meaning; the growing pressure on traditional hierarchical structures; parenting skills and the changing characteristics of a good coach?

Originality/value

Discusses ways of optimising coaching potential and proposes methods of practical coaching training.
Re‐defining careers in education
Authors: Rippon Janice H.
Published: July 2005

Purpose

To introduce the concept of diverse career cultures in the education system and to consider how these impact on individual career investment and attempts to modernise the teaching profession internationally.

Design/methodology/approach

A life history approach was used to determine the career environment of teachers, setting career theories and career policy against the lived experiences of a group of educationalists. The interaction of the structural, cultural and individual dimensions of career has been analysed using grounded theory to determine the emerging cultural themes.

Findings

Two distinct career cultures have emerged over time influencing how teachers perceive their work. Each career culture determines the career investment pattern of individuals regardless of the structural career promoted. For most teachers, a secure career culture is the dominant influence on career decision‐making despite the existence of a subordinate investment culture, more common to careers outside the education field.

Research limitations/implications

The concept of career culture should be explored with larger groups of teachers internationally and compared against other major occupational groups.

Practical implications

An investment career culture should be encouraged by re‐defining the modern career, the motivations of its members and the career sites open to them to promote diverse models of career investment.

Originality/value

This paper challenges the assumptions in current education policy that current structural changes will modernise the teaching career by looking at the subjective dimension of careers with potential recruits, existing educationalists and policy‐makers.
Who wants to be a mentor? An examination of attitudinal, instrumental, and social motivational components
Authors: Van Emmerik Hetty , Gayle Baugh S. , Euwema Martin C.
Published: July 2005

Purpose

This study investigates the influence of affective organizational commitment, career aspirations, and networking activities on propensity to mentor (serving as a mentor and desiring to become a mentor).

Design/methodology/approach

Data from websurveys of 262 managerial employees of a Dutch bank are analyzed using logistic regression.

Findings

Results indicate that affective organizational commitment is unrelated to propensity to mentor, whereas career aspirations are positively related, and networking activities are negatively related to serving as a mentor, but not desiring to be a mentor.

Research limitations/implications

The study is limited by its reliance on self‐report data and the Dutch culture may have influenced the results of the study to an unknown degree.

Practical implications

Results of this study suggest that employees volunteering to be a mentor are clearly ambitious in terms of their own career, but are not necessarily highly committed to their organization nor do they perform exemplary behaviors in terms of extra role behavior or networking.

Originality/value

Individuals are more likely to engage in mentoring activities and to desire to become a mentor if they have high career aspirations. This relationship may be the result of an instrumental perspective on the part of the mentor, who sees developing a cadre of loyal and supportive organizational members as having a positive effect on his or her own career advancement.
Evidence that the recessive bymovirus resistance locus rym4 in barley corresponds to the eukaryotic translation initiation factor 4E gene
Authors: KANYUKA KONSTANTIN , DRUKA ARNIS , CALDWELL DAVID G. , TYMON ANNA , MCCALLUM NICOLA , WAUGH ROBBIE , ADAMS MICHAEL J.
Published: July 2005

Recent studies have shown that resistance in several dicotyledonous plants to viruses in the genus Potyvirus is controlled by recessive alleles of the plant translation initiation factor eIF4E or eIF(iso)4E genes. Here we provide evidence that the barley rym4 gene locus, controlling immunity to viruses in the genus Bymovirus, corresponds to eIF4E. A molecular marker based on the sequence of eIF4E was developed and used to demonstrate that eIF4E and rym4 map to the same genetic interval on chromosome 3HL in barley. Another genetic marker was developed that detects a polymorphism in the coding sequence of eIF4E and consistently distinguishes between rym4 and susceptible barley cultivars of diverse parentage. The eIF4E gene product from barley genotypes carrying rym4 and allelic rym5 and rym6 genes, originating from separate exotic germplasm, and a novel resistant allele that we identified through a reverse genetics approach all contained unique amino acid substitutions compared with the wild‐type protein. Three‐dimensional models of the barley eIF4E protein revealed that the polymorphic residues identified are all located at or near the mRNA cap‐binding pocket, similarly to recent findings from studies on recessive potyvirus resistance in dicotyledonous plants. These new data complement our earlier observations that specific mutations in bymovirus VPg are responsible for overcoming rym4/5‐controlled resistance. Because the potyviral VPg is known to interact with eIF4E in dicotyledonous plants, it appears that monocotyledonous and dicotyledonous plants have evolved a similar strategy to combat VPg‐encoding viruses in the family Potyviridae.
Overview and analysis of the polyprotein cleavage sites in the family Potyviridae
Authors: ADAMS MICHAEL J. , ANTONIW JOHN F. , BEAUDOIN FREDERIC
Published: July 2005

The genomes of plant viruses in the family Potyviridae encode large polyproteins that are cut by virus‐encoded proteases into ten mature proteins. Three different types of protease have been identified, each of which cuts at sites with a distinctive sequence pattern. The experimental evidence for this specificity is reviewed and the cleavage site patterns are compiled for all sequenced species within the family. Seven of the nine cleavage sites in each species are cut by the viral NIa‐Pro and patterns around these sites are related where possible to the active site–substrate interactions recently deduced following the resolution of the crystal structure of Tobacco etch virus (TEV) NIa‐Pro (Phan et al., 2002. J. Biol. Chem. 277, 50564–50572). In particular, a revised series of cleavage sites for Sweet potato mild mottle virus (genus Ipomovirus) is proposed with a conserved His at the P1 position. This is supported by homology modelling studies using the TEV structure as a template. The data also provide a standard to correct the annotation of some other published sequences and to help predict these sites in further virus sequences as they become available. Comprehensive data for all sequences of each virus in the family, together with some summaries, have been made available at http://www.rothamsted.bbsrc.ac.uk/ppi/links/pplinks/potycleavage/index.html.
Pregnancy and its management in the Philadelphia negative myeloproliferative diseases
Authors: Harrison Claire
Published: July 2005

The myeloproliferative diseases (MPDs) present several therapeutic challenges in patients of childbearing potential. The most extensive literature exists for patients with essential thrombocythaemia, with over 200 pregnancies reported in retrospective case series. Yet there is conflicting data in relation to predicting pregnancy outcome and optimal management strategy. Pregnancy is less frequently reported for polycythaemia vera and myelofibrosis. There is a need for collaboration to further our knowledge in this field. Here, the literature is reviewed in detail and experience of different therapeutic strategies in pregnancy discussed. There is increasing understanding about the pathogenesis of placental dysfunction in inherited thrombophilia and antiphospholipid antibody syndrome pregnancy outcomes in these conditions parallel those reported for MPDs. Furthermore several large studies have influenced pregnancy management in these conditions and, whilst not directly applicable to MPDs, this data have potential to inform treatment protocols. This data are reviewed and a personal management strategy for pregnancy in MPD proposed.
Prognostic relevance of ‘early‐onset’ graft‐versus‐host disease following non‐myeloablative haematopoietic cell transplantation
Authors: Mielcarek Marco , Burroughs Lauri , Leisenring Wendy , Diaconescu Razvan , Martin Paul J. , Sandmaier Brenda M. , Maloney David G. , Maris Michael B. , Chauncey Thomas R. , Shizuru Judith A. , Blume Karl G. , Hegenbart Ute , Niederwieser Dietger , Forman Stephen , Bruno Benedetto , Woolfrey Ann , Storb Rainer
Published: July 2005

We retrospectively analysed outcomes among 395 patients with haematologic malignancies who underwent non‐myeloablative haematopoietic cell transplantation (HCT) from human leucocyte antigen (HLA)‐matched related (n = 297) or unrelated donors (n = 98) in order to identify a possible correlation between the time of onset of graft‐versus‐host disease (GVHD) and survival. The non‐myeloablative regimen consisted of 2 Gy total body irradiation with or without fludarabine, followed by postgrafting immunosuppression with mycophenolate mofetil and cyclosporine. The cumulative incidences of grades II–IV acute GVHD and extensive chronic GVHD were 45% and 47%, respectively, with related donors, and 68% and 68%, respectively, with unrelated donors. High‐dose corticosteroid treatment for acute or chronic GVHD was started at a median of 79 (range, 8–799) days and 30 (range, 5–333) days after transplantation from related and unrelated donors respectively. With related donors, the cumulative incidence of non‐relapse mortality among patients with GVHD was 55% at 4 years when prednisone was started before day 50 (n = 72), compared with 29% when treatment was started after day 50 (n = 115) (P < 0·001). With unrelated donors, time to onset of treatment for GVHD was not associated with survival. Patients with early‐onset GVHD after non‐myeloablative HCT from HLA‐identical related donors might benefit from intensified primary immunosuppressive treatment.
Prognosis of patients with acute myeloid leukaemia admitted to intensive care
Authors: Rabbat Antoine , Chaoui Driss , Montani David , Legrand Ollivier , Lefebvre Aurélie , Rio Bernard , Roche Nicolas , Lorut Christine , Marie Jean‐Pierre , Huchon Gérard
Published: July 2005

This retrospective study assessed the prognostic factors associated with early and long‐term outcome in consecutive patients with acute myeloid leukaemia (AML) admitted to the intensive care unit (ICU) over a 9‐year period. A total of 83 patients were studied (age 48 ± 16 years), among whom 60% were neutropenic on admission. For 68%, admission occurred within the first month following diagnosis of AML. The main reason for ICU admission was an acute respiratory disease in 82% of cases. Mechanical ventilation (MV) was required in 57% of patients. In‐ICU mortality was 34%. Among patients discharged alive from ICU, 49% died within a year after discharge. Factors significantly associated with in‐ICU death in multivariate analysis were simplified acute physiology score II and need for invasive MV (IMV). Age, performance status, AML3 subtype and complete remission were significantly associated with 1‐year survival. Patients with acute respiratory failure initially supported with non‐invasive MV had significantly better ICU outcome than patients initially supported with IMV. In conclusion, ICU admission is justified for selected patients with AML. The ICU mortality rate is highly predictable by the acute illness severity score. A 1‐year survival is predicted by haematological prognostic factors.
Targeting primary human leukaemia cells with RNA interference: Bcr‐Abl targeting inhibits myeloid progenitor self‐renewal in chronic myeloid leukaemia cells
Authors: Withey Jane ME , Marley Stephen B , Kaeda Jaspal , Harvey Amanda J , Crompton Mark R , Gordon Myrtle Y
Published: July 2005

We have investigated functional outcome of challenging primary chronic myeloid leukaemia (CML) cells with Bcr‐Abl fusion sequence‐directed RNA interference (RNAi). We targeted the Bcr‐Abl b3a2 variant, by RNAi, in primary chronic phase CML cells, and detected strikingly reduced proliferation of myeloid precursor cells expressing this variant. Lack of an effect in cells expressing a distinct Bcr‐Abl variant confirmed the specificity of the response. Through the functional targeting of an oncogene in primary human tumour cells, we have demonstrated that Bcr‐Abl enhances CML progenitor cell amplification, and that RNAi may be suitable for development as a specific anti‐leukaemia treatment.
Resolving and classifying haematopoietic bone‐marrow cell populations by multi‐dimensional analysis of flow‐cytometry data
Authors: Zamir Eli , Geiger Benjamin , Cohen Nir , Kam Zvi , Katz Ben‐Zion
Published: July 2005

The study of normal or malignant haematopoiesis requires the analysis of heterogeneous cell populations using multiple morphological and molecular criteria. Flow cytometry has the capacity to acquire multi‐parameter information of large haematopoietic cell populations, utilizing various combinations of >200 molecular markers (clusters of differentiation, CD). However, current flow cytometry analyses are based on serial gating of two‐parametric scatter plots – a process that is inherently incapable to discriminate all subgroups of cells in the data. Here we studied the cellular diversity of normal bone marrows (BM) using multi‐dimensional cluster analysis of six‐parametric flow cytometry data (four CD, forward scatter and side scatter), focusing mainly on the myeloid lineage. Twenty‐three subclasses of cells were resolved, many of them inseparable even when examined in all possible two‐parametric scatter plots. The multi‐dimensional analysis could distinguish the haematopoietic progenitors according to International Society of Haematotherapy and Graft Engineering criteria from other types of immature cells. Based on the defined clusters, we designed a classifier that assigns BM cells in samples to subclasses based on robust six‐dimensional position and extended shape. The analysis presented here can manage successfully both the increasing numbers of haematopoietic cellular markers and sample heterogeneity. This should enhance the ability to study normal haematopoiesis, and to identify and monitor haematopoietic disorders.
Identification of DKC1 gene mutations in Japanese patients with X‐linked dyskeratosis congenita
Authors: Kanegane Hirokazu , Kasahara Yoshihito , Okamura Jun , Hongo Teruaki , Tanaka Rieko , Nomura Keiko , Kojima Seiji , Miyawaki Toshio
Published: July 2005

Dyskeratosis congenita (DC) is a rare inherited multisystem disorder characterized by the triad of abnormal skin pigmentation, nail dystrophy and mucosal leucoplakia. X‐linked recessive inheritances are recognized in approximately 40% of the patients. DKC1 has been identified as the gene responsible for X‐linked DC, and genetic analyses have been performed in a worldwide study. Here, we performed genetic analysis of five Japanese patients with presumed X‐linked DC, and identified four mutations in the DKC1 gene, including two novel missense mutations (Q31K and T357A). Such genetic analysis is useful for the definite diagnosis and genetic counselling of patients.
Fusion hybrids of dendritic cells and autologous myeloid blasts as a potential cellular vaccine for acute myeloid leukaemia
Authors: Klammer M. , Waterfall M. , Samuel K. , Turner M. L. , Roddie P. H.
Published: July 2005

We assessed the potential of tumour cell/dendritic cell fusion hybrids to generate in vitro anti‐leukaemic T‐cell responses following co‐culture with autologous remission lymphocytes in six patients with acute myeloid leukaemia (AML). Comparison was made to anti‐leukaemic responses induced by mature dendritic cells (mDC) co‐cultured with autologous, irradiated myeloid blasts. Fusion hybrids induced anti‐leukaemic T‐cell immune responses in three of six patients. Tumour‐pulsed mDC induced T‐cellular responses in two other patients. Only one of six patients remission lymphocytes failed to develop leukaemia‐directed immune responses following stimulation with either construct. Anti‐proliferative properties of fusion hybrids against allogeneic lymphocytes were observed in mixed lymphocyte‐leukaemia reactions and were found not to be specific to the cell fusion partners and did not prevent the ability of AML–mDC heterokaryons to induce autologous anti‐leukaemic cytotoxicity. We conclude that tumour cell/dendritic cell fusion hybrids hold promise as a cellular vaccine for AML.
Epstein‐Barr virus‐associated familial Hodgkin lymphoma: paediatric onset in three of five siblings
Authors: Kamper Peter M. , Kjeldsen Eigil , Clausen Niels , Bendix Knud , Hamilton‐Dutoit Stephen , D'Amore Francesco
Published: July 2005

We report familial Hodgkin lymphoma (FHL) in a family with five children, of which three were human leucocyte antigen (HLA) class I identical. These three siblings were diagnosed with Epstein‐Barr virus (EBV)‐positive Hodgkin lymphoma within a 6‐year period. All three were treated with chemo‐ and/or radiotherapy and are presently in complete remission. None of the children had evidence of overt immunodeficiency or autoimmune disease. This case contributes to the existing material on FHL and implies a role for both HLA class I antigens and EBV infection of the tumour cell population in the pathogenesis of some cases of FHL.
Subtyping of natural killer cell cytotoxicity deficiencies in haemophagocytic lymphohistocytosis provides therapeutic guidance
Authors: Horne AnnaCarin , Zheng Chengyun , Lorenz Ingrid , Löfstedt Martina , Montgomery Scott M. , Janka Gritta , Henter Jan‐Inge , Marion Schneider E.
Published: July 2005

The familial form of haemophagocytic lymphohistiocytosis (HLH) is a fatal disease, with allogeneic stem cell transplantation (SCT) being the only curative treatment. In contrast, patients with secondary (infection‐associated) HLH usually do not require SCT. Since it often is difficult to distinguish primary and secondary HLH, we wanted to identify a tool that provides guidance on whether SCT is required. The clinical outcome of 65 HLH patients was analysed in relation to the recently reported four types of defects in natural killer (NK)‐cell cytotoxicity in HLH. None (0%) of the 36 patients with NK‐cell deficiency type 3 attained a sustained (1‐year) remission after stopping therapy without receiving SCT, in contrast to 45% (13/29) non‐type 3 patients (P < 0·001). Most type 3 patients (22/36) underwent SCT (14/22, 64% are alive), whereas 11 of 14 that did not receive SCT died, and the three others had received HLH‐therapy during the last year of follow‐up. Of 54 patients analysed for perforin expression and/or mutation, the five with perforin deficiency were all type 3 patients. The data suggests that HLH patients with NK‐cell deficiency type 3 will probably require SCT to survive. Thus, NK‐cell deficiency classification may provide valuable guidance in judging whether an HLH‐patient needs SCT.
Evidence for a link between sphingolipid metabolism and expression of CD1d and MHC‐class II: monocytes from Gaucher disease patients as a model
Authors: Balreira Andrea , Lacerda Lúcia , Miranda Clara Sá , Arosa Fernando A.
Published: July 2005

Gaucher disease (GD) is an autosomal recessive inherited defect of the lysosomal enzyme glucocerebrosidase (GluCerase) that leads to glucosylceramide (GluCer) accumulation. We previously demonstrated the existence of imbalances in certain lymphocyte populations in GD patients. We now show that GluCerase‐deficient monocytes from GD patients or monocytes from healthy subjects treated with conduritol‐B‐epoxide (CBE), an irreversible inhibitor of GluCerase activity, display high levels of surface expression of the lipid‐binding molecule CD1d. GluCerase‐deficient monocytes from GD patients also showed increased surface expression of major histocompatibility complex (MHC)‐class II, but not of other lysosomal trafficking molecules, such as CD63 and MHC‐class I. However, CD1d and MHC‐class II mRNA levels were not increased. GluCerase‐deficient monocytes from GD patients undergoing enzyme replacement therapy also exhibited increased levels of CD1d and MHC‐class II and imbalances in the percentage of CD4+, CD8+, and Vα24+T cells. Interestingly, follow‐up studies revealed that enzyme replacement therapy induced a decrease in MHC‐class II expression and partial correction of the CD4+T cell imbalances. These results reveal a new link between sphingolipid accumulation in monocytes and the expression of certain MHC molecules that may result in imbalances of regulatory T cell subsets. These immunological anomalies may contribute to the clinical heterogeneity in GD patients.
Polymorphisms in cytochrome P450 17A1 and risk of non‐Hodgkin lymphoma
Authors: Skibola Christine F. , Lightfoot Tracy , Agana Luz , Smith Alex , Rollinson Sara , Kao Andrew , Adamson Peter , Morgan Gareth J. , Smith Martyn T. , Roman Eve
Published: July 2005

Broad cross‐talk exists between the endocrine and immune systems. Estrogen receptor expression in lymphocytes suggests that hormonal modulation may influence lymphoma risk. Analysis of genetic polymorphisms that affect oestrogen production, such as cytochrome P450 17A1 (CYP17A1) −34T>C, may provide insight into oestrogen's role in lymphomagenesis. CYP17A1−34T>C and CYP17A1 IVS2 105A>C polymorphisms were analyzed in a non‐Hodgkin lymphoma (NHL) population‐based case–control study. The CYP17A1−34CC genotype was positively associated with NHL [odds ratio (OR) = 1·44, 95% confidence interval (CI) 1·02–2·03], particularly diffuse large B‐cell lymphoma (OR = 1·76, CI 1·14–2·71). Associations of CYP17A1 polymorphisms with increased risk of NHL suggest a role for oestrogen in lymphomagenesis.
Fusion of dendritic cells with multiple myeloma cells results in maturation and enhanced antigen presentation
Authors: Vasir Baldev , Borges Virginia , Wu Zekui , Grosman Daren , Rosenblatt Jacalyn , Irie Masaki , Anderson Kenneth , Kufe Donald , Avigan David
Published: July 2005

Dendritic cells (DCs) are potent antigen‐presenting cells that are uniquely capable of inducing primary immune responses. Although tumour cells may directly inhibit DC maturation, exposure to tumour products may also result in their activation. Fusions of cancer cells and DCs are being explored as cancer vaccines. The effect of tumour cell fusion on DC maturation and their functional characteristics has not been defined. In the present study, immature and mature DC generated from human CD34+ and peripheral blood precursors were fused to multiple myeloma cells in the presence of polyethylene glycol. Fusion of both immature and mature DCs with tumour cells resulted in an activated phenotype. In this regard, fusion cells expressed interleukin‐12, a cytokine essential for the induction of T‐helper cell type 1 immunity. In contrast to immature DCs, fusion cells also strongly expressed CC‐chemokine receptor R7, which is responsible for DC migration to draining lymph nodes. Fusions generated with both immature and mature DCs also potently stimulated T‐cell expression of γ‐interferon and cytotoxic T lymphocyte killing of tumour targets. These findings demonstrate that tumour cell fusion induces DC maturation and the development of an activated phenotype necessary for their effectiveness as cancer vaccines.