bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of basolateral chloride/bicarbonate exchange in macula densa cells
Authors: Komlosi Peter , Frische Sebastian , Fuson Amanda L. , Fintha Attila , Zsembery Ákos , Peti-Peterdi Janos , Bell P. Darwin
Published: October 2004

Functional and immunohistological studies were performed to identify basolateral chloride/bicarbonate exchange in macula densa cells. Using the isolated, perfused thick ascending limb with attached glomerulus preparation dissected from rabbit kidney, macula densa intracellular pH (pHi) was measured with fluorescence microscopy and BCECF. For these experiments, basolateral chloride was reduced, resulting in reversible macula densa cell alkalinization. Anion exchange activity was assessed by measuring the maximal net base efflux on readdition of bath chloride. Anion exchange activity required the presence of bicarbonate, was independent of changes in membrane potential, did not require the presence of sodium, and was inhibited by high concentrations of DIDS. Inhibition of macula densa anion exchange activity by basolateral DIDS increased luminal NaCl concentration-induced elevations in pHi. Immunohistochemical studies using antibodies against AE2 demonstrated expression of AE2 along the basolateral membrane of macula densa cells of rabbit kidney. These results suggest that macula densa cells functionally and immunologically express a chloride/bicarbonate exchanger at the basolateral membrane. This transporter likely participates in the regulation of pHiand might be involved in macula densa signaling.
Motor-Unit Activity Differs With Load Type During a Fatiguing Contraction
Authors: Mottram Carol J. , Jakobi Jennifer M. , Semmler John G. , Enoka Roger M.
Published: October 2004

Despite a similar rate of change in average electromyographic (EMG) activity, previous studies have observed different rates of change in mean arterial pressure, heart rate, perceived exertion, and fluctuations in motor output during the performance of fatiguing contractions that involved different types of loads. To obtain a more direct measure of the motor output from the spinal cord, the purpose of this study was to compare the discharge characteristics of the same motor unit in biceps brachii during the performance of two types of fatiguing contractions. In separate tests with the upper arm vertical and the elbow flexed to 1.57 rad, the seated subjects maintained either a constant upward force at the wrist (force task) or a constant elbow angle (position task) for a prescribed duration. The force and position tasks were performed in random order at a target force equal to 3.5 ± 2.1% (mean ± SD) of the maximal voluntary contraction (MVC) force above the recruitment threshold of the isolated motor unit. Each subject maintained the two tasks for an identical duration (161 ± 96 s) at a mean target force of 22.2 ± 13.4% MVC (range: 3–49% MVC). The dependent variables included the discharge characteristics of the same motor unit in biceps brachii, fluctuations in motor output (force or acceleration), mean arterial pressure, heart rate, and rating of perceived exertion. Despite similar increases in the amplitude of the averaged EMG (% MVC) for the elbow flexor muscles during both tasks ( P = 0.60), the rates of increase in mean arterial pressure ( P < 0.001), rating of perceived exertion ( P = 0.023), and fluctuations in motor output ( P = 0.003) were greater during the position task compared with the force task. Consistent with these differences, mean discharge rate declined at a greater rate during the position task ( P = 0.03), and the coefficient of variation for discharge rate increased only during the position task ( P = 0.02). Furthermore, more motor units were recruited during the position task compared with the force task ( P = 0.01). These findings indicate that despite a comparable net muscle torque, the rate of increase in the motor output from the spinal cord was greater during the position task.
Polymorphisms in the osteopontin promoter affect its transcriptional activity
Authors: Giacopelli Francesca , Marciano Renato , Pistorio Angela , Catarsi Paolo , Canini Silvana , Karsenty Gerard , Ravazzolo Roberto
Published: October 2004

Understanding the molecular mechanisms that underlie regulation of transcription of the human osteopontin encoding gene (OPN) may help to clarify several processes, such as fibrotic evolution of organ damage, tumorigenesis and metastasis, and immune response, in which OPN overexpression is observed. With the aim to evaluate variants with functional effect on transcription, we have analyzed the promoter region and focused our investigation on three common variants present in the first 500 bp upstream of the transcription start site. Transfection of constructs carrying the four most frequent haplotypes relative to variants at −66, −156, and −443 fused to the luciferase reporter gene in a panel of different cell lines showed that one haplotype conferred a significantly reduced level of reporter gene expression in all tested cell lines. We describe that the −66 polymorphism modifies the binding affinity for the SP1/SP3 transcription factors, the −156 polymorphism is included in a yet uncharacterized RUNX2 binding site, and the −443 polymorphism causes differential binding of an unknown factor. The finding of differential effects of various combination of variants in haplotypes may contribute to explain data of association studies reported in several already published articles. Future association studies using haplotypes instead of single OPN variants will allow to achieve more accurate results referable to differential expression of OPN in several common diseases, in which OPN is considered a candidate susceptibility gene.
Warfarin prophylaxis and venous thromboembolism in the first 5 days following hip and knee arthroplasty
Authors: Jaffer Amir , Hurbanek Jason , Morra Nariman , Brotman Daniel
Published: October 2004

Many orthopaedic surgeons use warfarin to prevent venous thromboembolism (VTE) following hip or knee arthroplasty. Since warfarin’s antithrombotic effects are delayed, we hypothesized that early VTE (occurring within 5 days post-operatively) would be more common in arthroplasty patients receiving warfarin monotherapy compared to those receiving enoxaparin. We performed a secondary analysis of a case-control study examining risk factors for post-operative thrombosis in postmenopausal women. We defined cases as patients who were diagnosed with thrombosis within 5 days of surgery. Controls without thrombosis were matched with cases by age, surgeon, year of surgery and surgical joint. 84 women with early post-operative thrombosis (cases) were matched with 206 controls. 18 cases (21.4%) had been prescribed warfarin monotherapy, compared with 7 controls (3.4%). 58 (69.1%) cases and 195 (94.7%) controls had been prescribed subcutaneous enoxaparin 30 mg twice daily, starting 12-24 hours after surgery. The odds ratio for any early thrombosis in patients receiving warfarin as opposed to enoxaparin 30 mg twice daily was 8.6 (p<0.0001). For proximal thrombosis, the odds ratio was 11.3 (p<0.0001). Multivariate analysis did not alter these findings. Warfarin’s delayed antithrombotic effects may not provide adequateVTE prophylaxis in the immediate post-operative setting. We suggest caution in employing warfarin monotherapy following joint arthroplasty.
Automobilities
Authors: Featherstone Mike
Published: October 2004

This wide-ranging introduction to the special issue on Automobilities examines various dimensions of the automobile system and car cultures. In its broadest sense we can think of many automobilities - modes of autonomous, self-directed movement. It can be argued that there are many different car cultures and autoscapes which operate around the world, which cannot be seen as making driving (including freeways, motorways and autobahns) a uniform experience of movement in a controlled 'no-place' space. Yet, there clearly is an increasingly globalizing car system, conceptualized as a powerful socio-economic and technological complex which sustains the car as a key object of mass production (Fordism) and mass consumption, which has impacted on spatial organization through roads, city layout, suburban housing and shopping malls and demands new forms of social life, sociability and time-space flexibility. This automobile system currently accounts for some 1.2 million deaths through traffic accidents a year world-wide, with the reversal of the long normalization of this form of 'mass murder,' now seen as a key topic for public health authorities. At the same time while it is potentially possible to subject cars to greater surveillance and systemic control through information technology, this in itself may not automatically lead to a reduction of accidents. In recent years the car has become a complex communicative platform for multi-tasking, a command centre for telephone, television, Internet etc., a place of work and instrumental tasking; but also a place of dwelling and refuge, a comfort zone for emotional decontrol via the sound system. Something which requires a more flexible driving habitus in which the senses are reconfigured and extended through the technology, as driving increasingly depends on the software as we move to intelligent cars and roads. Yet this is also something which generates an expanding set of new risks. The logic is for the driver to become the auto pilot and the automobile to become a sort of datasuit wrap. Yet it is not surprising that this view of the controlled safe car should also summon up its opposite: the car as dangerous and powerful, as a vehicle for excitement and speed. Especially so given that car racing practically originated alongside the birth of the automobile and is now itself a massive global industry whose imagery is central to the marketing of many types of cars.
Driving in the City
Authors: Thrift Nigel
Published: October 2004

This article argues that de Certeau’s understanding of walking as the archetypal transhuman practice of making the city habitable cannot hold in a post-human world. By concentrating on the practices of driving, I argue that other experiences of the city can have an equal validity. In other words, de Certeau’s work on everyday life in the city needs to be reworked in order to take into account the rise of automobility. The bulk of this article is devoted to exploring how that goal might be achieved, concentrating in particular on how new knowledge like software and ergonomics has become responsible for a large-scale spatial reordering of the city which presages an important change in what counts as making the city habitable.
The Driver-car
Authors: Dant Tim
Published: October 2004

The car has become ubiquitous in late modern society and has become the leading object in the ordinary social relations of mobility. Despite its centrality to the culture and material form of modern societies, the relationship between the car and human beings has remained largely unexplored by sociology. This article argues that cars are combined with their drivers into an assemblage, the ‘driver-car’, which has become a form of social being that brings about distinctive social actions in modern society – driving, transporting, parking, consuming, polluting, killing, communicating and so on. To understand the nature of this assemblage a number of theoretical perspectives that describe the interaction and collaboration between human beings and complex objects are explored; the process of driving, ‘affordance’, actor-network theory, and the embodied relationship between driver and car. This theoretical account of the driver-car is intended as a preliminary to the empirical investigation of the place of the driver-car in modern societies.
Automobility and National Identity
Authors: Edensor Tim
Published: October 2004

Accounts of the nation and national identity have tended to focus upon the transmission by cultural elites of authoritative culture, invented traditions and folk customs. Following Billig, I suggest that the national is increasingly located in the everyday and in the realm of popular culture; far more so than in ‘high’ and ‘official’ forms of culture. To exemplify this, I discuss national automobilities, specifically exploring the role of iconic models, mundane motorscapes and the everyday, habitual performances of driving. With a particular focus upon British and Indian car cultures, I further suggest that the ‘national’ is not a singular or monolithic entity but is constituted out of a vast matrix of interrelated elements, three of which are the models, geographies and performances identified above. As the national proliferates and expands, becoming globalized, it generates multiple forms of national identity, although consistencies and points of focus remain. Accordingly, as in other cultural fields, I argue that while global manifestations of automobility proliferate, this has not necessarily diminished the salience of the national in the relationship between driving cars and identity. The national thus remains a powerful constituent of identity precisely because of its often unreflexive grounding in everyday spaces and practices.
Cars and Nations
Authors: Koshar Rudy
Published: October 2004

This article argues that historically specific, transnational structures and conjunctures influence the car’s national belongingness. Neither historians nor sociologists have devoted sufficient attention to how the automobile mediates cultural processes in general and national identification in particular, the article maintains. Using a British motoring journalist’s observations on the 1928 Berlin Auto Show, the discussion explores how the Mercedes worked as a symbol of German automotive tradition, a marker of international relations between Britain and Germany, and a spur to anxieties about the effects of mass production techniques and US automobility for both countries. The article then turns to small cars, demonstrating that the British observer’s embrace of German and Continental small-car design belied longer-term anxieties about the level and nature of British automobility, while simultaneously mirroring German dissatisfactions and hopes regarding the potential for mass auto ownership in the form of the Volkswagen. If cars in some sense ‘belong’ to nations, the study concludes, then it is important to stress how the continuities and discontinuities that condition such belongingness often work across national borders in historically unique combinations.
Driving Places
Authors: Merriman Peter
Published: October 2004

In this article I provide a critical account of the ‘placing’ of England’s M1 motorway. I start by critiquing Marc Augé’s anthropological writings on ‘non-places’ which have provided a common point of reference for academics discussing spaces of travel, consumption and exchange in the contemporary world. I argue that Augé’s ethnology of supermodernity results in a rather partial account of these sites, that he overstates the novelty of contemporary experiences of these spaces, and that he fails to acknowledge the heterogeneity and materiality of the social networks bound up with the production of non-places/places. I suggest that, rather than focusing on the presences and absences associated with the polarities of place and non-place, academics should examine the multiple, partial, dynamic and relational ‘placings’ which arise through the diverse performances and movements associated with travel, consumption and exchange. I then trace the topologies of England’s M1 motorway, examining some of the different ways in which the motorway has been assembled, performed and placed over the past 45 years.
Three Ages of the Automobile
Authors: Gartman David
Published: October 2004

The automobile as an object of consumption, carrying meanings and identities, has evolved through three ages during the 20th century, each characterized by a peculiar cultural logic. In the age of class distinction, the car served as a status symbol of the sort theorized by Pierre Bourdieu. It marked out differences between classes, while simultaneously misrecognizing and legitimating their origins. In the age of mass individuality, the car was a reified consumer commodity, as postulated by the theory of the Frankfurt School. It served to obscure qualitative class differences underneath the illusion of mass individuality, in which consumers varied by the quantity of desired automotive traits they could afford. In the age of subcultural difference, the car expressed the different identities of lifestyle groups in a leveled and pluralized consumer culture, as theorized by postmodernism. The extension of the cultural logic of each of these automotive ages ultimately contradicted its configuration, and pushed the car forward to the next age.
Auto Couture
Authors: Inglis David
Published: October 2004

The automobile has figured as an important issue of concern and a profound source of fascination for a wide range of intellectuals in France since the 1950s. The car has been understood variously as a covert vehicle of creeping Americanization and consumerization, a threatening object that obliterates nature, a harbinger of hyper-modern futures, and as a constitutive element of everyday practices. This article traces out the diverse ways in which the car has been ‘good to think with’ for a range of French intellectuals in the period spanning roughly from 1950 through to the 1970s. It seeks to demonstrate the richness of those currents of thought in post-war France which were concerned to comprehend the nature of car cultures. It is argued that these ways of thinking can be drawn upon in the present day by those wishing to analyse contemporary features of automobility.
Automobility and the Power of Sound
Authors: Bull Michael
Published: October 2004

This article analyses the connections between forms of solitary automobile habitation and the use of mobile sound technologies in automobiles: the radio, cassette, sound system and mobile phone. It does this through an empirically informed analysis of automobile use. In doing so it re-evaluates our understanding of the occupation of space and place, arguing that traditional concepts of urban space have underestimated the active role that the users of these communication technologies might have in transforming the meaning of these spaces as they pass through them. The article points to the powerful, and potentially problematic, role that sound technologies play in the daily experience of moving through the city.
Doing Office Work on the Motorway
Authors: Laurier Eric
Published: October 2004

This article takes the motorway seriously as a place where the society of traffic can be found and studied. While many kinds of activities are done by drivers and passengers in parallel with driving on the motorway, such as listening to the radio, eating lunch or caring for, or being, children, I focus here on office work. Empirical material from a video-ethnography of one driver doing paperwork and overtaking a slow-moving vehicle ahead is used to examine in detail some of the practices of combining driving and office-duties in the car while in motion. Drawing on the work of Harvey Sacks, the article examines how this mobile society is naturally organized as an architectural configuration brought to life in the practices of driving in traffic. Overlooked phenomena that are orderly stable features of being mobile are analysed, such as ‘overtaking’, ‘tailgating’ and ‘cruising’. Where other writers have used ‘speed’ to theorize the contemporary period, a brief re-specification is offered in the light of the uses, moral and otherwise, of speed within, and as made apprehensible in relation to, traffic.
Constructing social representations of science and technology: the role of metaphors in the press and the popular scientific magazines
Authors: Christidou Vasilia , Dimopoulos Kostas , Koulaidis Vasilis
Published: October 2004

This paper aims to reveal the social representations about the nature and the evolution of Space-Science & Astronomy, Genetics & Biotechnology, Natural Sciences and Engineering & Informatics, through analyzing active (i.e., original and creative) metaphors found in 2303 technoscientific articles published in four Greek daily newspapers and two popular scientific magazines. The analysis showed that all metaphors concerning the nature of the four disciplinary fields can be clustered into four superordinate categories that juxtapose these fields to: (1) a construct; (2) a supernatural process; (3) an activity extending the frontiers of knowledge; (4) a dipole of promise and/or scare. The most frequently employed category is that representing technoscience as an activity extending the frontiers of knowledge. Furthermore, the evolution of the four disciplines is mainly represented as a violent process. Each discipline though, seems to be characterized by combinations of different categories of metaphors. Therefore each discipline evokes different social representations.
The meat of the matter: grasping and judging xenotransplantation
Authors: Michael Mike , Brown Nik
Published: October 2004

This paper is concerned with the ways in which lay people come to understand and assess xenotransplantation. Drawing on focus group data, we explore how people can both demonstrate a collective process of cost–benefit thinking and tacitly problematize this by deploying three meta-arguments that we call “trust,” “telos,” and “trump.” Respectively, these meta-arguments emphasize: unexamined relations of trust; irrelevance because innovations such as xenotransplantation are inevitable; and redundancy in the face of desperation. We then consider how lay people draw upon certain analogies associated with meat in order to grasp the meaning of xenotransplantation. The data show how “meat” itself displays disparate and contested meanings. Depending on what aspects of meat are emphasized, xenotransplantation is represented in either a negative or a positive light. Some of the implications of the fluidity of the meaning of both meat and xenotransplantation for cost– benefit thinking in lay and expert discourse are discussed.
Stories of the “medicine cow”: representations of future promises in media discourse
Authors: Väliverronen Esa
Published: October 2004

This paper studies the changing media representations and public perceptions of biotechnology through a case study of the generation of transgenic cattle in Finland. The particular focus is on rhetoric of the future: the narrative shaping of future promises, the politics of naming, visual images, and the role of the news media in producing and circulating images of new genetics. It is suggested that scientists can play a dominant role in popularizing scientific and technological innovations by using positive metaphors and visual imagery of genetics.
Sahaja Yoga Meditation as a Family Treatment Programme for Children with Attention Deficit-Hyperactivity Disorder
Authors: Harrison Linda J. , Manocha Ramesh , Rubia Katya
Published: October 2004

The use of complementary and alternative medicine (CAM) as a treatment for children diagnosed with attention deficit-hyperactivity disorder (ADHD) is widespread, but little is known on the effectiveness of many such therapies. This study investigated meditation as a family treatment method for children with ADHD, using the techniques of Sahaja Yoga Meditation (SYM). Parents and children participated in a 6-week programme of twice-weekly clinic sessions and regular meditation at home. Pre- and post-treatment assessments included parent ratings of children’s ADHD symptoms, self-esteem and child–parent relationship quality. Perceptions of the programme were collected via parent questionnaires and child interviews. Results showed improvements in children’s ADHD behaviour, self-esteem and relationship quality. Children described benefits at home (better sleep patterns, less anxiety) and at school (more able to concentrate, less conflict). Parents reported feeling happier, less stressed and more able to manage their child’s behaviour. Indications from this preliminary investigation are that SYM may offer families an effective management tool for family-oriented treatment of childhood ADHD.
A Group-Work Approach to Addressing Friendship Issues in the Treatment of Adolescents with Eating Disorders
Authors: Davies Sarah
Published: October 2004

People with eating disorders often have some associated social difficulties. Given that friendships are of particular importance during adolescence, and that maintaining friendships during in-patient admission seems to aid the process of rehabilitation, there is a need for interventions that address friendship issues to form part of in-patient treatment programmes for adolescents with eating disorders. A group-work approach has been identified to address friendship issues within this context. The rationale for a Friends Group, key elements of the group and related issues are discussed. Patients’ experiences are reported and case examples provided to illustrate the function and value of the group.
Non-Directive Play Therapy for Young Children with Autism: A Case Study
Authors: Josefi Orit , Ryan Virginia
Published: October 2004

This article presents exploratory research on the feasibility of non-directive play therapy for children with autism. Video recordings of 16 sessions of play therapy with a 6-year-old boy with severe autism were analysed qualitatively and quantitatively. The study concluded that this child was able to enter into a therapeutic relationship and demonstrated attachment behaviour towards the therapist. Key areas of improvement were in the child’s development of autonomy and pretend play, while ritualistic behaviours showed only mild improvement. Changes in therapy were concurrent with the changes reported by the boy’s mother at home of increased independence and empathy. One implication of this preliminary research is that non-directive play therapy may enhance and accelerate emotional/social development of children with severe autism. More research is urgently needed; non-directive play therapy and behavioural treatments may complement one another to provide an overall treatment plan for children with severe autism.
A Brief Overview of the Principles of Psychotherapy with Asperger’s Syndrome
Authors: Jacobsen Paula
Published: October 2004

People with Apserger’s syndrome understand and respond to the world in a very different way from other people. Individual psychotherapy can be an important approach, in addition to other therapies and case management, for children with Asperger’s syndrome. A frame of reference for the therapeutic relationship with Asperger individuals is described. This addresses the perspective of those with Asperger’s as well as the perspective of others in their lives. The cognitive concepts theory of mind, central coherence, and executive functioning are briefly reviewed with an emphasis on how they help us to understand the Asperger mind, and with examples of their presentation and use in clinical assessment and psychotherapy. Perspective, intention, and awareness, as they relate to the therapeutic interventions, are illustrated with brief vignettes.
Adolescent Perceptions of Meaningfulness of Psychiatric Hospitalization
Authors: Grossoehme Daniel H. , Gerbetz Lawrence
Published: October 2004

Positive patient outcomes are related to patient satisfaction and the meaningfulness of their hospital experience. Limited attention has been paid to how adolescent psychiatric in-patients experience their treatment course. This study was developed to examine how hospitalized adolescents experience the treatment milieu during an acute hospitalization in a crisis stabilization unit. The study consisted of a survey administered to 105 in-patients at the time of their discharge from the unit. The most meaningful experiences were those in which adolescents focused on issues related to hospitalization and learned skills for breaking problems down into manageable pieces which included setting realistic and achievable goals. Males and females did not significantly differ in their experience of the unit. Identifying the adolescents’ needs and teaching them goal-setting appears to be very important in acute in-patient care. Adolescents reported peer contact and goal-setting work to be the most meaningful experiences.
Refining control balance theory
Authors: Tittle Charles R.
Published: October 2004

This article proposes revisions to control balance theory to address a logical flaw, mistaken categorization, and inconsistencies and conceptual ambiguity in the original formulation, and it attempts to accommodate empirical findings that challenge some of its premises. The reformulated theory addresses three forms of behavior—conformity, deviance and submission—and introduces the concept of ‘control balance desirability’ to help resolve some issues in the original formulation.
Theorizing the penality of sentencing in international criminal trials
Authors: Henham Ralph
Published: October 2004

This article seeks to make a contribution towards resolving the theoretical and methodological challenges posed by the increasing internationalization of criminal trial process and the pressing need to provide concepts and methodological techniques that will enhance our understanding of the global, regional and domestic effects of these developments. However, in order to achieve this objective it is necessary to develop concepts and methods capable of revealing the true nature and meaning of what is actually taking place at the various decision sites in the trial at all levels. The article explains how the novel approach of comparative contextual analysis can be used to provide insights into the relationship between the process of discretionary decision-making and sentencing outcomes in international criminal trials and help provide us with the analytical tools required to deconstruct the international sentencing process and influence the future direction of its penality.
Security in ambiguity
Authors: de Lint Willem , Virta Sirpa
Published: October 2004

In this article we offer a reconceptualization of security that attempts to reconcile a post-critical and normative agenda. The article proceeds by unpacking features of the dominant security discourse and then resituating the question in a radical politics. We contend that moving forward on this question requires a rejection of the association between security, certainty and authority. Rather than following the classical realist view that security requires exceptions from politics, we choose to see security as dependent on political uncertainty. Borrowing from Häanninen’s idea that politics is ‘living with ambiguity’ and taking from post-Foucauldian thought against the violence of tyranny, we advocate the ongoing repoliticization of the security field informed by harm reduction. We offer ‘security in ambiguity’ as a conceptualization of this synthesis.
Butyrate increases the efficiency of translation of γ-globin mRNA
Authors: Weinberg Rona S. , Ji Xinjun , Sutton Millicent , Perrine Susan , Galperin Yelena , Li Qiliang , Liebhaber Stephen A. , Stamatoyannopoulos George , Atweh George F.
Published: October 2004

Fetal hemoglobin (Hb F) levels increase in most patients with sickle cell disease following intermittent butyrate therapy. Although the full effects of butyrate on Hb F levels usually require multiple treatment cycles, in some patients a peak level is achieved after a few days of butyrate therapy. Our investigation of the mechanism(s) responsible for this rapid induction of Hb F by butyrate showed that reticulocyte γ-globin chain synthesis markedly increased within 24 hours of butyrate exposure, without concomitant changes in reticulocyte γ-globin mRNA levels. This suggests that butyrate might induce Hb F by increasing the efficiency of translation of γ-globin mRNA. This hypothesis was confirmed by ribosome loading studies that demonstrated enrichment of the polysomal fraction of reticulocytes with γ-globin mRNA following butyrate exposure. Thus, the induction of Hb F by butyrate may be mediated by translational effects in addition to its well-known effects on transcription of the γ-globin genes. (Blood. 2005;105:1807-1809)
Meis1-mediated apoptosis is caspase dependent and can be suppressed by coexpression of HoxA9 in murine and human cell lines
Authors: Wermuth Peter J. , Buchberg Arthur M.
Published: October 2004

Coexpression of the homeodomain protein Meis1 and either HoxA7 or HoxA9 is characteristic of many acute myelogenous leukemias. Although Meis1 can be overexpressed in bone marrow long-term repopulating cells, it is incapable of mediating their transformation. Although overexpressing HoxA9 alone transforms murine bone marrow cells, concurrent Meis1 overexpression greatly accelerates oncogenesis. Meis1-HoxA9 cooperation suppresses several myeloid differentiation pathways. We now report that Meis1 overexpression strongly induces apoptosis in a variety of cell types in vitro through a caspase-dependent process. Meis1 requires a functional homeodomain and Pbx-interaction motif to induce apoptosis. Coexpressing HoxA9 with Meis1 suppresses this apoptosis and provides protection from several apoptosis inducers. Pbx1, another Meis1 cofactor, also induces apoptosis; however, coexpressing HoxA9 is incapable of rescuing Pbx-mediated apoptosis. This resistance to apoptotic stimuli, coupled with the previously reported ability to suppress multiple myeloid differentiation pathways, would provide a strong selective advantage to Meis1-HoxA9 coexpressing cells in vivo, leading to leukemogenesis.
Tissue inhibitor of metalloproteinase 1 (TIMP-1) promotes plasmablastic differentiation of a Burkitt lymphoma cell line: implications in the pathogenesis of plasmacytic/plasmablastic tumors
Authors: Guedez Liliana , Martinez Antonio , Zhao Shumei , Vivero Angelica , Pittaluga Stefania , Stetler-Stevenson Maryalice , Raffeld Mark , Stetler-Stevenson William G.
Published: October 2004

Tissue inhibitor of metalloproteinase 1 (TIMP-1) is a stromal factor with multiple functions. Overexpression of TIMP-1 correlates with aggressive clinical behavior of a spectrum of tumors. Here, for the first time, we address the role of TIMP-1 in the pathogenesis of B-cell lymphomas. An Epstein-Barr virus (EBV)-negative Burkitt lymphoma cell line with ectopic TIMP-1 expression (TIMP-1JD38) was used to identify genes induced/repressed by TIMP-1. Differentially expressed genes were analyzed by cDNA microarray, and they were validated by immunohistochemistry, flow cytometry, and Western blotting. Analysis revealed changes of genes coding for B-cell growth/differentiation, transcription, and cell cycle regulators. TIMP-1 repressed expression of germinal center (GC) markers CD10, Bcl-6, PAX-5 and up-regulated plasma cell-associated antigens CD138, MUM-1/IRF-4, XBP-1, and CD44, suggesting a plasma cell differentiation. This is accompanied by activation of signal transducer and activator of transcription 3 (STAT-3) and switch to cyclin D2 expression. However, TIMP-1JD38 cells expressed an inactive form of XBP-1, lacking antibody production/secretion. This incomplete plasmacytic differentiation occurs without altering cell proliferation, and despite c-Myc deregulation, indicating an arrested plasmacytic/plasmablastic stage of differentiation. Further validation in human lymphoma cell lines and in primary B-cell tumors demonstrated a predominant TIMP-1 expression in tumors with plasmacytic/plasmablastic phenotypes, including multiple myelomas. These findings strongly support TIMP-1 as an important factor in the pathogenesis of plasmacytic/plasmablastic tumors. (Blood. 2005;105:1660-1668)
Impaired T- and B-cell development in Tcl1-deficient mice
Authors: Kang Sang-Moo , Narducci Maria Grazia , Lazzeri Cristina , Mongiovì Adriana M. , Caprini Elisabetta , Bresin Antonella , Martelli Fabio , Rothstein Jay , Croce Carlo Maria , Cooper Max D. , Russo Giandomenico
Published: October 2004

TCL1, the overexpression of which may result in T-cell leukemia, is normally expressed in early embryonic tissues, the ovary, and lymphoid lineage cells. Our analysis of mouse B-lineage cells indicates that Tcl1 expression is initiated in pro-B cells and persists in splenic marginal zone and follicular B cells. T-lineage Tcl1 expression begins in thymocyte progenitors, continues in CD4+CD8+ thymocytes, and is extinguished in mature T cells. In Tcl1-deficient mice, we found B lymphopoiesis to be compromised at the pre-B cell stage and T-cell lymphopoiesis to be impaired at the CD4+CD8+ thymocyte stage. A corresponding increase was observed in thymocyte susceptibility to anti-CD3ϵ–induced apoptosis. Reduced numbers of splenic follicular and germinal center B cells were accompanied by impaired production of immunoglobulin G1 (IgG1) and IgG2b antibodies in response to a T-dependent antigen. The marginal zone B cells and T-cell–independent antibody responses were also diminished in Tcl1-/- mice. This analysis indicates a significant role for Tcl1, a coactivator of Akt signaling, in normal T- and B-cell development and function.
Hepcidin excess induces the sequestration of iron and exacerbates tumor-associated anemia
Authors: Rivera Seth , Liu Lide , Nemeth Elizabeta , Gabayan Victoria , Sorensen Ole E. , Ganz Tomas
Published: October 2004

The iron-regulatory hormone hepcidin has been proposed as the mediator of anemia of inflammation (AI). We examined the acute and chronic effects of hepcidin in the mouse. Injections of human hepcidin (50 μg/mouse), but not of its diluent, induced hypoferremia within 4 hours. To examine the chronic effects of hepcidin, we implanted either tumor xenografts engineered to overexpress human hepcidin or control tumor xenografts into nonobese diabetic-severe combined immunodeficiency (NOD-SCID) mice. Despite abundant dietary iron, mice with hepcidin-producing tumors developed more severe anemia, lower serum iron, and increased hepatic iron compared with mice with control tumors. Hepcidin contributes to AI by shunting iron away from erythropoiesis and sequestering it in the liver, predominantly in hepatocytes. (Blood. 2005;105:1797-1802)
Overdispersed logistic regression for SAGE: Modelling multiple groups and covariates
Authors: Baggerly Keith A , Deng Li , Morris Jeffrey S , Aldaz C Marcelo
Published: October 2004

Background

Two major identifiable sources of variation in data derived from the Serial Analysis of Gene Expression (SAGE) are within-library sampling variability and between-library heterogeneity within a group. Most published methods for identifying differential expression focus on just the sampling variability. In recent work, the problem of assessing differential expression between two groups of SAGE libraries has been addressed by introducing a beta-binomial hierarchical model that explicitly deals with both of the above sources of variation. This model leads to a test statistic analogous to a weighted two-sample t-test. When the number of groups involved is more than two, however, a more general approach is needed.

Results

We describe how logistic regression with overdispersion supplies this generalization, carrying with it the framework for incorporating other covariates into the model as a byproduct. This approach has the advantage that logistic regression routines are available in several common statistical packages.

Conclusions

The described method provides an easily implemented tool for analyzing SAGE data that correctly handles multiple types of variation and allows for more flexible modelling.
Extending the mutual information measure to rank inferred literature relationships
Authors: Wren Jonathan D
Published: October 2004

Background

Within the peer-reviewed literature, associations between two things are not always recognized until commonalities between them become apparent. These commonalities can provide justification for the inference of a new relationship where none was previously known, and are the basis of most observation-based hypothesis formation. It has been shown that the crux of the problem is not finding inferable associations, which are extraordinarily abundant given the scale-free networks that arise from literature-based associations, but determining which ones are informative. The Mutual Information Measure (MIM) is a well-established method to measure how informative an association is, but is limited to direct (i.e. observable) associations.

Results

Herein, we attempt to extend the calculation of mutual information to indirect (i.e. inferable) associations by using the MIM of shared associations. Objects of general research interest (e.g. genes, diseases, phenotypes, drugs, ontology categories) found within MEDLINE are used to create a network of associations for evaluation.

Conclusions

Mutual information calculations can be effectively extended into implied relationships and a significance cutoff estimated from analysis of random word networks. Of the models tested, the shared minimum MIM (MMIM) model is found to correlate best with the observed strength and frequency of known associations. Using three test cases, the MMIM method tends to rank more specific relationships higher than counting the number of shared relationships within a network.
Patterns of Schistosoma haematobium infection, impact of praziquantel treatment and re-infection after treatment in a cohort of schoolchildren from rural KwaZulu-Natal/South Africa
Authors: Saathoff Elmar , Olsen Annette , Magnussen Pascal , Kvalsvig Jane D , Becker Wilhelm , Appleton Chris C
Published: October 2004

Background

Schistosomiasis is one of the major health problems in tropical and sub-tropical countries, with school age children usually being the most affected group. In 1998 the Department of Health of the province of KwaZulu-Natal established a pilot programme for helminth control that aimed at regularly treating primary school children for schistosome and intestinal helminth infections. This article describes the baseline situation and the impact of treatment on S. haematobium infection in a cohort of schoolchildren attending grade 3 in a rural part of the province.

Methods

Primary schoolchildren from Maputaland in northern KwaZulu-Natal were examined for Schistosoma haematobium infection, treated with praziquantel and re-examined four times over one year after treatment in order to assess the impact of treatment and patterns of infection and re-infection.

Results

Praziquantel treatment was highly efficacious at three weeks after treatment when judged by egg reduction rate (95.3%) and cure rate of heavy infections (94.1%). The apparent overall cure rate three weeks after treatment (57.9%) was much lower but improved to 80.7% at 41 weeks after treatment. Re-infection with S. haematobium was low and appeared to be limited to the hot and rainy summer. Analysis of only one urine specimen per child considerably underestimated prevalence when compared to the analysis of two specimens, but both approaches provided similar estimates of the proportion of heavy infections and of average infection intensity in the population.

Conclusion

According to WHO guidelines the high prevalence and intensity of S. haematobium infection necessitate regular treatment of schoolchildren in the area. The seasonal transmission pattern together with the slow pace of re-infection suggest that one treatment per year, applied after the end of summer, is sufficient to keep S. haematobium infection in the area at low levels.
Assessing the impact of humanitarian assistance in the health sector
Authors: Roberts Les , Hofmann Charles-Antoine
Published: October 2004

There have been significant improvements in the design and management of humanitarian aid responses in the last decade. In particular, a significant body of knowledge has been accumulated about public health interventions in emergencies, following calls for developing the evidence base of humanitarian health interventions. Several factors have prompted this, such as the increased volume of humanitarian assistance with subsequent higher levels of scrutiny on aid spending, and greater pressure for improving humanitarian aid quality and performance. However, documentation of the ability of humanitarian interventions to alleviate suffering and curb mortality remains limited. This paper argues that epidemiological studies can potentially be a useful tool for measuring the impact of health interventions in humanitarian crises. Survey methods or surveillance systems are mainly used for early warning or needs assessment and their potential for assessing the impact of aid programmes is underutilised.
The role of the applied epidemiologist in armed conflict
Authors: McDonnell Sharon M , Bolton Paul , Sunderland Nadine , Bellows Ben , White Mark , Noji Eric
Published: October 2004

Background

Applied epidemiologists are increasingly working in areas of insecurity and active conflict to define the health risks, suggest feasible means to reduce these risks and, monitor the capacity and reconstruction of the public health system. In 2001, The Carter Center and the United States Institute for Peace sponsored a conference within which "Violence and Health" was discussed and a working group on applied epidemiology formed. The group was tasked to describe the skills that are essential to effective functioning in these settings and thereby provide guidance to the applied epidemiology training programs.

Methods

We conducted a literature review and consultation of a convenience sample of practitioners of applied epidemiology with experience in conflict areas.

Results and conclusions

The health programs designed to prevent and mitigate conflict are in their early stages of implementation and the evaluation measures for success are still being defined. The practice of epidemiology in conflict must occur within a larger humanitarian and political context to be effective. The skills required extend beyond the normal epidemiological training that focuses on the valid collection and interpretation of data and fall into two general categories: (1) Conducting a thorough assessment of the conflict setting in order to design more effective public health action in conflict settings, and (2) Communicating effectively to guide health program implementation, to advocate for needed policy changes and to facilitate interagency coordination. These are described and illustrated using examples from different countries.
External Causes of Pediatric Injury‐related Emergency Department Visits in the United States
Authors: Simon Tamara D. , Bublitz Caroline , Hambidge Simon J.
Published: October 2004

Objectives: To characterize the types and external causes of pediatric injury‐related visits (IRVs) to emergency departments (EDs), in particular, sports‐related injuries. To compare the characteristics of children with IRVs with those with non‐IRVs, specifically, differences in IRV rates by race and ethnicity and by health insurance. Methods: This was a stratified random‐sample survey of EDs in the National Hospital Ambulatory Medical Care Survey (NHAMCS), including all IRVs for patients less than 19 years of age in 1998 (n= 2,656). National estimates of pediatric IRVs were obtained using the assigned patient visit weights in the NHAMCS databases and SUDAAN analyses. Measures of association between predictor variables (patient and health insurance characteristics) and whether a child had an IRV were calculated using multivariate logistic regression analyses to determine adjusted odds ratios with 95% confidence intervals. Results: Pediatric IRVs accounted for more than 11 million ED visits annually. The most common diagnoses for IRVs were open wounds, contusions, sprains and strains, and fractures and dislocations. The leading external causes of IRVs were sports‐related injuries, accidental falls, being struck by objects, and motor vehicle collisions. Children with IRVs differed from those who presented for non‐IRVs in many characteristics: they were more likely to be male, to be older, to be of white race, and to have private insurance, and less likely to be of Asian or Hispanic ethnicity. Conclusions: Sports and recreation are the leading external causes of pediatric IRVs to EDs in the United States. There are different patterns of IRVs according to gender, age, race, ethnicity, and insurance. Identification of specific patterns of injury is necessary for the design of effective prevention strategies.