bluuebunny/crossref_metadata_2025 huggingface dataset:
Cronenberg, Greenaway and the Ideologies of Twinship
Authors: GOMEL ELANA , WENINGER STEPHEN
Published: September 2003

This article deals with the representation of identical twins in the films Zed and Two Noughts by Peter Greenaway and Dead Ringers by David Cronenberg. It situates the films in a cultural and political context of the 20th-century controversies surrounding the issues of evolution, reproduction and cloning. The article claims that twinship represents the corporeal economy of the Same, whose ideological meanings have been shaped by the history of eugenics and social Darwinism. Identical twinship inscribes a utopia of the perfect, unchanging and self-identical body, opposed to the unpredictability, confusion and contingency of sexual reproduction and evolutionary history. The films under discussion critique the utopian ideology of twinship and its imaginary cancellation of difference as narcissistic and deadly.
The Naked Subject: Nudity, Context and Sexualization in Contemporary Culture
Authors: COVER ROB
Published: September 2003

This article examines the ways in which contemporary western cultures have attempted to legitimize certain sites of bodily nakedness (such as communal showers, bathing children and other `public' displays) by maintaining a contextual space or frame which attempts to exclude the sexual. Noting the ways in which that legitimacy has broken down in recent decades, the article suggests that the slippage between the sexual and the naked results from both a breakdown in the `heterosexual matrix' as well as a postmodern crisis of `the context'.
Of Shit and the Soul: Tropes of Cybernetic Disembodiment in Contemporary Culture
Authors: MURI ALLISON
Published: September 2003

Since the 1980s, popular media, literature and theory have suggested that technology has induced a newly evolved, posthuman and postmodern cyborg consciousness. This article examines the premise of human evolution towards a disembodied `post-human' state in cyberpunk literature and film, as well as some influential cyber-theory. Rather than indicating a revolutionary change in human consciousness, both cyber-lit and cybertheory incorporate and reinscribe Western Christian narratives about human identity. Images of disembodiment tend to reaffirm traditional religious concepts of human reproduction, individual consciousness, spirit and body, and life after death.
Shaping e-Access in the Cybercafé: Networks, Boundaries and Heterotopian Innovation
Authors: Liff Sonia , Steward Fred
Published: September 2003

The cybercafé is located as an innovative site of e-access emerging in the 1990s. Accounts of its novelty are reviewed. Its distinctiveness as a site linking the `real' and the `virtual' is theorized in terms of social networks and Foucault's concept of heterotopia. The growth and nature of cybercafés in the UK are investigated using data from a number of surveys. The detailed practices of a sample of cybercafés are examined using data from on-site interviews and observations. It is shown that the properties of a heterotopia are expressed in cybercafés, but to differing degrees explained by contrasting types of boundary-spanning practice. It argued that this analysis has implications for the future management and facilitation of e-access in cybercafés.
Involvement in (the Information) Society - The Joensuu Community Resource Centre Netcafé
Authors: Uotinen Johanna
Published: September 2003

Finland is said to be at the forefront of information society development. However, the rhetoric has been deterministic, presenting an inevitable phenomenon to which all citizens have to adapt. There has been a tendency to ignore all social, regional and local differences. The province of North Karelia aspires to be a more citizen-oriented information society. The Joensuu Community Resource Centre (CRC) Netcafé is a place which provides the opportunity (but not the necessity) for spontaneous involvement and participation in (the information) society. It creates space for local interpretations and views about information society and technology. The research is based on a questionnaire and interviews. When information technology is combined with the CRC's various other activities, it cannot be an independent, self-governed phenomenon. The CRC provides a context that allows a sense of proportion to develop in relation to information technology and the rhetoric of information society strategy.
The Embedding of Local Culture in Global Communication: Independent Internet Cafés in London
Authors: Wakeford Nina
Published: September 2003

Although public internet access in London is dominated by the large chain easy Internet Cafe, outside the central areas many small independent internet cafés are catering to local populations. This article examines the ways in which two of these cafés operate. Participant observation and interviews provide the data for this study of the ways in which both the local and the global are embedded into the internet cultures which are found in such settings. Patterns of migration and local demographics are found to be just as important as the layout of the space or the technological infrastructure. It is suggested that these spaces merit more study and that the standardized easy Internet café should not become the dominant unit of analysis for the study of London internet cafés, despite its significant presence in the city.
Show Your Real Face
Authors: Jones Janet Megan
Published: September 2003

This audience research was designed to interrogate the UK fans of Big Brother so as to present evidence that might shed light on the audience's understanding of the `reality' in this form of reality television. Using quantitative and qualitative data obtained from a web-based questionnaire linked to Big Brother's UK web site over three years, I investigate how the fan audiences negotiate what I have called `personalised reality contracts' with the contributors, and how this affects their understanding of what they are seeing as `real' or `constructed'. I argue that it is Big Brother's constructedness that serves to liberate its content, allowing the viewer freedom to navigate past the performative elements typical of the docu-soap genre. I outline how this form of multi-platform TV creatively involves viewers on a number of levels, allowing them to develop strategies for watching that satisfy the desire to witness `the real' through the lens of the camera. This is set within the context of the larger debate surrounding the change in status of factual programming.
Violence, Suffering and Human Rights
Authors: Hastrup Kirsten
Published: September 2003

This article develops a trenchant critique of the rise of human rights as the main universal standard against which to judge violence and suffering. It begins with a case study of an act of mass atrocity in Surinam that was brought before the Inter-American Court of Human Rights and which demonstrates the ways in which rights-based conceptions of justice distort our understandings of suffering and pare down social and moral narratives. Legal language instrumentalizes, cutting out the symbolic and expressive dimensions of violence. Anthropology is opposed to this methodological individualist and positivist approach to representation as it seeks to understand people's life worlds experientially. In contrast, the article asserts that violence is always a social fact, which can be apprehended through inter-subjectivity and dialogue in the Bakhtinian sense. Conversation, understood in this manner, can provide an alternative to the `epistemological dictatorship' of a censorious rights-based regime of truth, and also of an anthropological discourse based in `culture'.
Voices Twice Silenced
Authors: West Harry G.
Published: September 2003

In the course of gathering life histories in northern Mozambique, the author encountered men who had been the victims of torture at the hands of the Portuguese during the Mozambican war for independence. The author gives an account of his conversations with these men, reflecting upon the urgency with which they told him their stories decades after their experience of violence. Where Portuguese attempts to `rehabilitate' political prisoners and to use them as counterinsurgency operatives rendered all torture victims suspect in the eyes of the post-independence state, and where the atmosphere of political suspicion was exacerbated by civil war, these men were frustrated in their attempts to find a public discursive space in which to make sense of what had happened to them. They consequently spoke of their experiences as if mourning their own deaths, the author argues, while demanding as recently departed ancestors that they not be forgotten.
A Survey of Self-Advocacy Groups for People with Learning Disabilities in an English Region
Authors: Mcnally Steve
Published: September 2003

This is the second article on the development, implementation and analysis of a survey of self-advocacy groups for people with learning disabilities in the midlands region of England. One hundred questionnaires were posted to groups and 53 were completed — a good response for remote work with groups whose members may not read. In postal surveys non-response can be overestimated because ineligible or unreachable respondents may be regarded as refusals. Three respondents identified themselves as ineligible; therefore the response rate was no less than 54 percent. Groups provided information about their origins, structure and functioning. Among the key findings were the consistency of the issues identified as important, and the willingness to engage in research. The overwhelming majority of groups indicated that they would participate further in the project. Participatory research paradigms from the social model of disability can enhance our understanding of self-advocates' experience.
The impact of donor KIR and patient HLA-C genotypes on outcome following HLA-identical sibling hematopoietic stem cell transplantation for myeloid leukemia
Authors: Cook Mark A. , Milligan Donald W. , Fegan Christopher D. , Darbyshire Philip J. , Mahendra Premini , Craddock Charles F. , Moss Paul A. H. , Briggs David C.
Published: September 2003

Killer immunoglobulin–like receptors (KIRs) regulate cell activity of natural killer (NK) cells and some T cells. The predominant ligand for inhibitory KIRs is HLA-C, which subdivides into 2 groups based on the specificity of inhibitory KIRs. The ligands for activatory KIRs are unknown. Following hematopoietic stem cell transplantation (HSCT), recipient tissues may not express a ligand for KIRs present within the graft, and the combination of donor KIR and recipient HLA-C types could influence outcome. HLA and KIR genotypes were determined in 220 donor-recipient pairs from HLA-matched sibling HSCTs performed for myeloid (n = 112) and lymphoid (n = 108) diseases. In HSCTs performed for myeloid disease, overall survival was worse in patients homozygous for group 2 HLA-C (C2) than in patients who carried a group 1 HLA-C (C1) allele (P < .005). Moreover, this effect is seen only when the donor additionally carries the activating KIR gene KIR2DS2 (P = .045). No effect was seen in patients with lymphoid disease. Thus, in HLA-matched sibling HSCT for myeloid leukemia, patients homozygous for C2 alleles receiving a graft from a donor carrying the KIR gene KIR2DS2 have a significantly reduced chance of survival.
Successful hematopoietic stem cell transplantation for Fanconi anemia from an unaffected HLA-genotype–identical sibling selected using preimplantation genetic diagnosis
Authors: Grewal Satkiran S. , Kahn Jeffrey P. , MacMillan Margaret L. , Ramsay Norma K. C. , Wagner John E.
Published: September 2003

The only proven cure for Fanconi anemia (FA)-associated bone marrow failure is successful allogeneic hematopoietic stem cell transplantation (HSCT). However, HSCT with donors other than HLA-identical siblings is associated with high morbidity and poor survival. Therefore, we used preimplantation genetic diagnosis (PGD) to select an embryo produced by in vitro fertilization (IVF) that was unaffected by FA and was HLA-identical to the proband. The patient was a 6-year-old girl with FA and myelodysplasia previously treated with oxymetholone and prednisone. After her parents underwent 5 cycles of IVF with intrauterine transfer of 7 embryos over a span of 4 years, successful pregnancy ensued. Twenty-eight days after delivery, the patient underwent transplantation with her newborn sibling donor's HLA-identical umbilical cord blood hematopoietic stem cells (HSCs). Neutrophil recovery occurred on day 17 without subsequent acute or chronic graft-versus-host disease. Currently, 2.5 years after transplantation, the patient is well and hematopoiesis is normal. In summary, we have described the first successful transplantation, using IVF and PGD, of HSCs from a donor selected on the basis of specific, desirable disease and HLA characteristics. The medical, legal, and ethical issues involved with this approach are discussed. (Blood. 2004;103:1147-1151)
Telomere length and telomerase activity delineate distinctive replicative features of the B-CLL subgroups defined by immunoglobulin V gene mutations
Authors: Damle Rajendra N. , Batliwalla Franak M. , Ghiotto Fabio , Valetto Angelo , Albesiano Emilia , Sison Cristina , Allen Steven L. , Kolitz Jonathan , Vinciguerra Vincent P. , Kudalkar Prasad , Wasil Tarun , Rai Kanti R. , Ferrarini Manlio , Gregersen Peter K. , Chiorazzi Nicholas
Published: September 2003

Patients with B-cell chronic lymphocytic leukemia (B-CLL) segregate into subgroups with very different survival times. Because clinical observations suggest that leukemic cells accumulate at different rates, we measured telomere length and telomerase activity in B-CLL cells to distinguish differences in cellular replication. Our data indicate that the telomeres of B-CLL cells are shorter than telomeres of B cells from healthy subjects, indicating that the leukemic cells have a prolonged proliferative history. Leukemic cells of the immunoglobulin V gene mutation subgroups differ in telomere length and telomerase activity. B lymphocytes from the subgroup with poor outcome and with limited IgV gene mutations have uniformly shorter telomeres and more telomerase activity than those from the subgroup with better outcome and with considerable mutations. Differences in telomere length appear to largely reflect the proliferative histories of precursors of the leukemic cells, although differences in cell division, masked by the action of telomerase, cannot be excluded. These results may provide insight into the stages of maturation and the activation pathways of the cells that give rise to B-CLL. In addition, they reinforce the concept that B-CLL is not simply an accumulative disease of slowly dividing B lymphocytes but possibly one of B cells with extensive proliferative histories.
CD44-hyaluronic acid interactions mediate shear-resistant binding of lymphocytes to dermal endothelium in acute cutaneous GVHD
Authors: Milinkovic Mirjana , Antin Joseph H. , Hergrueter Charles A. , Underhill Charles B. , Sackstein Robert
Published: September 2003

For circulating lymphocytes to migrate to inflammatory sites, they must first adhere to the target tissue endothelium with sufficient strength to overcome the shear forces of blood flow. We previously reported that dermal papillary vessels in acute graft-versus-host disease (aGVHD) support shear-resistant lymphocyte adherence. We now identify the relevant adhesion molecule(s) directing this binding, showing that interactions between lymphocyte CD44 and hyaluronic acid (HA) expressed on dermal vessels in aGVHD alone confer this shear-resistant attachment. Native HA deposits on vascular endothelium support lymphocyte adherence, whereas HA immobilized on plastic does not. HA expressed at dermal endothelium in aGVHD is thus specialized to support lymphocyte adherence under flow conditions, and CD44-HA interactions may contribute to lymphocytotropism to skin in aGVHD.
Platelets are necessary for airway wall remodeling in a murine model of chronic allergic inflammation
Authors: Pitchford Simon C. , Riffo-Vasquez Yanira , Sousa Ana , Momi Stefania , Gresele Paolo , Spina Domenico , Page Clive P.
Published: September 2003

Asthma is associated with airway remodeling. Evidence of platelet recruitment to the lungs of asthmatics after allergen exposure suggests platelets participate in various aspects of asthma; although their importance is unknown in the context of airway remodeling, their involvement in atherosclerosis is established. Studies from our laboratory have shown a requirement for platelets in pulmonary leukocyte recruitment in a murine model of allergic lung inflammation. Presently, the effects of platelet depletion and corticosteroid administration on airway remodeling and lung function were examined. Ovalbumin (OVA)–sensitized mice, exposed to aerosolized OVA for 8 weeks, demonstrated epithelial and smooth muscle thickening, and subepithelial reticular fiber deposition in the distal airways. The depletion of platelets via an immunologic (antiplatelet antisera) or nonimmunologic (busulfan) method, markedly reduced airway remodeling. In contrast, dexamethasone administration did not affect epithelial thickening or subepithelial fibrosis, despite significantly inhibiting leukocyte recruitment. Thus, pathways leading to certain aspects of airway remodeling may not depend on leukocyte recruitment, whereas platelet activation is obligatory. OVA-sensitized mice exhibited airway hyperresponsiveness (AHR) compared with shamsensitized mice following chronic OVA exposure. Neither platelet depletion nor dexamethasone administration inhibited chronic AHR; thus, mechanisms other than inflammation and airway remodeling may be involved in the pathogenesis of chronic AHR.
Cyclophosphamide metabolism is affected by azole antifungals
Authors: Marr Kieren A. , Leisenring Wendy , Crippa Fulvio , Slattery John T. , Corey Lawrence , Boeckh Michael , McDonald George B.
Published: September 2003

We performed a randomized trial to compare the safety and efficacy of itraconazole with fluconazole in preventing fungal infections in patients undergoing allogeneic stem cell transplantation (SCT). Itraconazole (intravenous 200 mg daily, or oral solution 2.5 mg/kg 3 times daily) and fluconazole (intravenous or oral, 400 mg daily) were administered with the start of conditioning therapy, until at least 120 days after SCT. After enrollment of the first 197 patients, a data and safety monitoring board reviewed potential drug-related toxicities. Patients who received itraconazole developed higher serum bilirubin and creatinine values in the first 20 days after SCT, with highest values in patients who received itraconazole concurrent with cyclophosphamide (CY) conditioning. Analysis of CY metabolism in a subset of patients demonstrated higher exposure to toxic metabolites among recipients of itraconazole compared with fluconazole. These data suggest that azole antifungals, through differential inhibition of hepatic cytochrome P-450 isoenzymes, affect CY metabolism and conditioning-related toxicities.
Combined deficiency of protease-activated receptor-4 and fibrinogen recapitulates the hemostatic defect but not the embryonic lethality of prothrombin deficiency
Authors: Camerer Eric , Duong Daniel N. , Hamilton Justin R. , Coughlin Shaun R.
Published: September 2003

The availability of the relevant mutant mouse lines provided an opportunity to test the doctrine that platelet activation and fibrin formation account for the importance of thrombin for hemostasis. Prothrombin-deficient mice that survive to birth exsanguinate in the perinatal period. By contrast, protease-activated receptor 4 (PAR4)–deficient mice, which have platelets that fail to respond to thrombin, survive to adulthood with only a mild bleeding diathesis, and fibrinogen-deficient mice show perinatal bleeding but those that survive this period can have a relatively normal life expectancy. We now report that mice that lacked both PAR4 and fibrinogen exsanguinated at birth like prothrombin-deficient mice. However, while approximately half of prothrombindeficient embryos die during midgestation, mice lacking both PAR4 and fibrinogen developed normally. At face value, these results suggest that platelet activation and fibrin formation are together sufficient to account for the importance of thrombin for hemostasis but not for its importance for embryonic development.
Functional overlap of GATA-1 and GATA-2 in primitive hematopoietic development
Authors: Fujiwara Yuko , Chang Aaron N. , Williams Aimée M. , Orkin Stuart H.
Published: September 2003

Transcription factors GATA-1 and GATA-2 are required for normal hematopoiesis. The loss of either leads to embryonic lethality in knockout mice because of the failure of erythroid maturation and the expansion of progenitors, respectively. As the expression of GATA-1 and GATA-2 overlaps within hematopoietic progenitors, the extent to which these factors functionally compensate for each other during embryogenesis is unknown. As shown here, we have analyzed double-knockout embryos at the yolk sac stage of development and have shown that the combined absence of these GATA factors virtually ablates primitive erythroid cell formation. Thus, the function of GATA-1 and GATA-2 overlaps at the yolk sac stage. Moreover, a GATA factor, either GATA-1 or GATA-2, is required to initiate blood formation in the embryo.
Long-Term Treatment with Insulin Induces Apoptosis in Brown Adipocytes: Role of Oxidative Stress
Authors: Porras Almudena , Zuluaga Susana , Valladares Amparo , Álvarez Alberto M. , Herrera Blanca , Fabregat Isabel , Benito Manuel
Published: September 2003

Trying to define the precise role played by insulin regulating the survival of brown adipocytes, we have used rat fetal brown adipocytes maintained in primary culture. The effect of insulin on apoptosis and the mechanisms involved were assessed. Different from the known effects of insulin as a survival factor, we have found that long-term treatment (72 h) with insulin induces apoptosis in rat fetal brown adipocytes. This process is dependent on the phosphatidylinositol 3-kinase/mammalian target of rapamycin/p70 S6 kinase pathway. Short-term treatment with the conditioned medium from brown adipocytes treated with insulin for 72 h mimicked the apoptotic effect of insulin. During the process, caspase 8 activation, Bid cleavage, cytochrome c release, and activation of caspases 9 and 3 are sequentially produced. Treatment with the caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp (Z-VAD), prevents activation of this apoptotic cascade. The antioxidants, ascorbic acid and superoxide dismutase, also impair this process of apoptosis. Moreover, generation of reactive oxygen species (ROS), probably through reduced nicotinamide adenine dinucleotide phosphate oxidases, and a late decrease in reduced glutathione content are produced. According to this, antioxidants prevent caspase 8 activation and Bid cleavage, suggesting that ROS production is an important event mediating this process of apoptosis. However, the participation of uncoupling protein-1, -2, and -3 regulating ROS is unclear because their levels remain unchanged upon insulin treatment for 72 h. Our data suggest that the prolonged hyperinsulinemia might cause insulin resistance through the loss of brown adipose tissue.
Hedgehog signaling is directly required for the development of zebrafish dorsal root ganglia neurons
Authors: Ungos Josette M. , Karlstrom Rolf O. , Raible David W.
Published: September 2003

Hedgehog (Hh) signal transduction is directly required in zebrafish DRG precursors for proper development of DRG neurons. Zebrafish mutations in the Hh signaling pathway result in the absence of DRG neurons and the loss of expression of neurogenin1 (ngn1), a gene required for determination of DRG precursors. Cell transplantation experiments demonstrate that Hh acts directly on DRG neuron precursors. Blocking Hh pathway activation at later stages of embryogenesis with the steroidal alkaloid, cyclopamine,further reveals that the requirement for a Hh signal response in DRG precursors correlates with the onset of ngn1 expression. These results suggest that Hh signaling may normally promote DRG development by regulating expression of ngn1 in DRG precursors.
Slb/Wnt11 controls hypoblast cell migration and morphogenesis at the onset of zebrafish gastrulation
Authors: Ulrich Florian , Concha Miguel L. , Heid Paul J. , Voss Ed , Witzel Sabine , Roehl Henry , Tada Masazumi , Wilson Stephen W. , Adams Richard J. , Soll David R. , Heisenberg Carl-Philipp
Published: September 2003

During vertebrate gastrulation, highly coordinated cellular rearrangements lead to the formation of the three germ layers, ectoderm, mesoderm and endoderm. In zebrafish, silberblick (slb)/wnt11regulates normal gastrulation movements by activating a signalling pathway similar to the Frizzled-signalling pathway, which establishes epithelial planar cell polarity (PCP) in Drosophila. However, the cellular mechanisms by which slb/wnt11 functions during zebrafish gastrulation are still unclear. Using high-resolution two-photon confocal imaging followed by computer-assisted reconstruction and motion analysis, we have analysed the movement and morphology of individual cells in three dimensions during the course of gastrulation. We show that in slb-mutant embryos, hypoblast cells within the forming germ ring have slower, less directed migratory movements at the onset of gastrulation. These aberrant cell movements are accompanied by defects in the orientation of cellular processes along the individual movement directions of these cells. We conclude that slb/wnt11-mediated orientation of cellular processes plays a role in facilitating and stabilising movements of hypoblast cells in the germ ring,thereby pointing at a novel function of the slb/wnt11 signalling pathway for the regulation of migratory cell movements at early stages of gastrulation.
Even-skipped, acting as a repressor, regulates axonal projections inDrosophila
Authors: Fujioka Miki , Lear Bridget C. , Landgraf Matthias , Yusibova Galina L. , Zhou Jian , Riley Kristen M. , Patel Nipam H. , Jaynes James B.
Published: September 2003

Nervous system-specific eve mutants were created by removing regulatory elements from a 16 kb transgene capable of complete rescue of normal eve function. When transgenes lacking the regulatory element for either RP2+a/pCC, EL or U/CQ neurons were placed in an eve-null background, eve expression was completely eliminated in the corresponding neurons, without affecting other aspects of eveexpression. Many of these transgenic flies were able to survive to fertile adulthood. In the RP2+a/pCC mutant flies: (1) both RP2 and aCC showed abnormal axonal projection patterns, failing to innervate their normal target muscles;(2) the cell bodies of these neurons were positioned abnormally; and (3) in contrast to the wild type, pCC axons often crossed the midline. The Eve HD alone was able to provide a weak, partial rescue of the mutant phenotype,while both the Groucho-dependent and -independent repressor domains contributed equally to full rescue of each aspect of the mutant phenotype. Complete rescue was also obtained with a chimeric protein containing the Eve HD and the Engrailed repressor domain. Consistent with the apparent sufficiency of repressor function, a fusion protein between the Gal4 DNA-binding domain and Eve repressor domains was capable of actively repressing UAS target genes in these neurons. A key target of the repressor function of Eve was Drosophila Hb9, the derepression of which correlated with the mutant phenotype in individual eve-mutant neurons. Finally, homologues of Eve from diverse species were able to rescue the eve mutant phenotype, indicating conservation of both targeting and repression functions in the nervous system.
ER export of ERGIC-53 is controlled by cooperation of targeting determinants in all three of its domains
Authors: Nufer Oliver , Kappeler Felix , Guldbrandsen Svend , Hauri Hans-Peter
Published: September 2003

Selective export of proteins from the endoplasmic reticulum (ER) requires transport signals that have not been fully characterized. Here, we provide the first complete map of ER export determinants of a type I membrane protein, ERGIC-53, that cycles in the early secretory pathway. ER export requires a phenylalanine motif at the C-terminus, known to mediate coat protein II (COPII) interaction, that is assisted by a glutamine in the cytoplasmic domain. Disulfide bond-stabilized oligomerization is also required. Efficient hexamerization depends on the presence of a polar and two aromatic residues in the transmembrane domain (TMD). Oligomerization becomes independent on disulfide bonds when TMD hydrophobicity is increased. ER export is also influenced by TMD length, 21 amino acids being most efficient. When transferred to a signal-less construct, the established targeting motifs reconstitute full transport activity. The results suggest an ER-export mechanism in which transmembrane and luminal determinants mediate oligomerization required for efficient recruitment of ERGIC-53 into budding vesicles via the C-terminal COPII-binding phenylalanine motif.
Prime-boost strategies for malaria vaccine development
Authors: Dunachie Susanna J. , Hill Adrian V. S.
Published: September 2003

Malaria is an intracellular pathogen, for which an effective vaccine is likely to require induction of cell-mediated immunity. Immunisation approaches that stimulate strong and persistent levels of effector T-cells are being sought by many researchers. DNA vaccines, recombinant protein and viral vectors were amongst the vaccine delivery systems that appeared promising for the generation of cellular immunity, and in some initial studies in small animals this goal was achieved. However, clinical trials of these candidate vaccines when used alone or in repeated homologous boosting regimes have been disappointing, with short-lived low levels of induced specific T-cell responses. Recent years have seen the development of immunisation strategies using a combination of different antigen delivery systems encoding the same epitopes or antigen, delivered at an interval of a few weeks apart. This sequential immunisation approach with different vectors is known as heterologous prime-boosting and is capable of inducing greatly enhanced and persistent levels of CD8+ T-cells and Th1-type CD4+ T-cells compared to homologous boosting. This review will summarise the key pre-clinical studies of prime-boost strategy and outline recent progress in clinical trials of this approach. Possible mechanisms of action and potential improvements to existing delivery systems will be discussed. The prime-boost approach represents an encouraging step towards establishing an effective preventative vaccine to one of the world's greatest killers.
Progress in the development of recombinant and synthetic blood-stage malaria vaccines
Authors: Mahanty Siddhartha , Saul Allan , Miller Louis H.
Published: September 2003

The use of asexual blood-stage proteins as malaria vaccines is strongly supported by experimental data directly implicating antibodies induced by these antigens in parasite clearance and protection from re-challenge. The selection of blood-stage antigens is based on their ability to interfere with the pathogenesis of clinical malaria by reducing parasitemias. These vaccines could complement other vaccines aimed at preventing infection, such as those targeted at pre-erythrocytic or mosquito stages of the parasite. Asexual blood-stage vaccines may reduce disease by blockade of red blood cell invasion, inhibition of parasite growth in red cells or interference in cytoadherence of infected red cells. Clearance of blood-stage parasites is dependent primarily on antibody-mediated mechanisms, but CD4 T cells may also play an important role in help for B cells and probably have a direct effector function in the clearance of blood-stage parasites. Since asexual blood-stage parasites reside within erythrocytes, they are accessible to immune clearance mechanisms only for a short time, which imposes special requirements on vaccines. For example, immunity that induces high titers of antibody will be required. Antigenic variation and extensive polymorphism of malarial proteins also needs to be addressed. Several recombinant antigens derived from blood-stage proteins have moved beyond basic research and are now poised for phase I trials in endemic countries. In this review we discuss the state of asexual blood-stage vaccines, focusing on recombinant antigens from Plasmodium falciparum. The significance of polymorphism and antigenic variation, the relevance of parasite immune evasion mechanisms, the need for reliable measures of successful intervention and new adjuvants are reviewed. Results from trials of asexual blood stage vaccine that support the continued effort to develop these antigens as key ingredients of multicomponent,multistage malaria vaccines are documented.
Removal of well-fixed, cementless, acetabular components in revision hip arthroplasty
Authors: Mitchell P. A. , Masri B. A. , Garbuz D. S. , Greidanus N. V. , Wilson D. , Duncan C. P.
Published: September 2003

Removal of well-fixed, cementless, acetabular components during revision arthroplasty remains a challenging problem. Further damage to host bone may limit options for reconstruction and compromise the long-term result of the revision operation. We report the results of 31 hips with well-fixed, cementless sockets which were removed using a new cup extraction system. In all hips the socket was removed without difficulty and with minimal further bone loss.
Histological evaluation of chondral defects after autologous chondrocyte implantation of the knee
Authors: Briggs T. W. R. , Mahroof S. , David L. A. , Flannelly J. , Pringle J. , Bayliss M.
Published: September 2003

We have performed a prospective, single-surgeon study analysing the histological results of autologous chondrocyte implantation.

Fourteen patients underwent autologous chondrocyte implantation of the knee and were evaluated at one year by clinical assessment and arthroscopy. Standard staining was used to examine the sections. In addition, in situ hybridisation was used to establish type-IIa and type-IIb collagen mRNA expression and immunolocalisation techniques demonstrated the positions of type-II and type-X collagen.

Eight patients regenerated hyaline cartilage and also contained type-X collagen in the deepest layers and type-II collagen in the deep layers. Three demonstrated fibrocartilage and had type-II collagen in the deep layers. In situ hybridisation revealed that all 14 samples had the potential to express both type-IIa and type-IIb collagen.

We have shown that one year after the initial implantation chondrocytes are capable of producing type-II collagen and that they continue to proliferate and mature.
Quality of life 20 years after arthrodesis of the ankle
Authors: Fuchs S. , Sandmann C. , Skwara A. , Chylarecki C.
Published: September 2003

Tibiotalar fusion is considered to be the standard treatment for end-stage post-traumatic arthritis of the ankle. We report a retrospective, objective long-term study of the quality of life of 17 patients with 18 arthrodeses of the ankle, over a period of more than 20 years. We looked particularly for correlation between clinical and radiological signs of osteoarthritis in adjoining joints. At serial physical examinations, clinical grades were awarded according to the Olerud Molander Ankle (OMA) score. Any degree of degenerative change in the adjoining joints was recorded on standing radiographs. Patients filled out a SF-36 Health Survey form.

Subjectively, 50% of patients were not handicapped in the performance of daily activities and 44% were in the same job as at the time of injury. At follow-up the mean OMA score was 59.4 points, the visual analogue scale was 1.99 and the radiological score was 2.7. The SF-36 for physical function, emotional disturbance and bodily pain revealed significant deficits. There was a significant correlation between the OMA and the radiological score (p = 0.05), and between the clinical and the SF-36 score (p = 0.01), but no significant correlation between the radiological score and the SF-36 score.

Arthrodesis of the ankle leads to deficits in the functional outcome, to limitations in the activities of daily living and to radiological changes in the adjoining joints. The clinical outcome score correlates closely with the SF-36 score.
Relative anterior spinal overgrowth in adolescent idiopathic scoliosis
Authors: Guo X. , Chau W.-W. , Chan Y.-L. , Cheng J. C.-Y.
Published: September 2003

We undertook a comparative study of magnetic resonance imaging (MRI) vertebral morphometry of thoracic vertebrae of girls with adolescent idiopathic thoracic scoliosis (AIS) and age and gender-matched normal subjects, in order to investigate abnormal differential growth of the anterior and posterior elements of the thoracic vertebrae in patients with scoliosis. Previous studies have suggested that disproportionate growth of the anterior and posterior columns may contribute to the development of AIS. Whole spine MRI was undertaken on 83 girls with AIS between the age of 12 and 14 years, and Cobb’s angles of between 20° and 90°, and 22 age-matched controls. Multiple measurements of each thoracic vertebra were obtained from the best sagittal and axial MRI cuts. Compared with the controls, the scoliotic spines had longer vertebral bodies between T1 and T12 in the anterior column and shorter pedicles with a larger interpedicular distance in the posterior column. The differential growth between the anterior and the posterior elements of each thoracic vertebra in the patients with AIS was significantly different from that in the controls (p < 0.01). There was also a significant positive correlation between the scoliosis severity score and the ratio of differential growth between the anterior and posterior columns for each thoracic vertebra (p < 0.01). Compared with age-matched controls, the longitudinal growth of the vertebral bodies in patients with AIS is disproportionate and faster and mainly occurs by endochondral ossification. In contrast, the circumferential growth by membranous ossification is slower in both the vertebral bodies and pedicles.
Infection after total hip arthroplasty
Authors: Blom A. W. , Taylor A. H. , Pattison G. , Whitehouse S. , Bannister G. C.
Published: September 2003

Our aim in this study was to determine the outcome of hip arthroplasty with regard to infection at our unit. Infection after total joint arthroplasty is a devastating complication. The MRC study in 1984 recommended using vertical laminar flow and prophylactic antibiotics to reduce infection rates. These measures are now routinely used. Between 1993 and 1996, 1727 primary total hip arthroplasties and 305 revision hip arthroplasties were performed and 1567 of the primary and 284 of the revision arthroplasties were reviewed between five and eight years after surgery by means of a postal questionnaire, telephone interview or examination of the medical records of those who had died.

Seventeen (1.08%) of the patients who underwent primary and six (2.1%) of those who underwent revision arthroplasty had a post-operative infection. Only 0.45% of patients who underwent primary arthroplasty required revision for infection.

To our knowledge this is the largest multi-surgeon audit of infection after total hip replacement in the UK. The follow-up of between five and eight years is longer than that of most comparable studies. Our study has shown that a large cohort of surgeons of varying seniority can achieve infection rates of 1% and revision rates for infection of less than 0.5%.
A study of the mechanical and electrical properties of a polymer/carbon black binder system used in battery electrodes
Authors: Chen Zonghai , Christensen L. , Dahn J. R.
Published: September 2003

The effects of carbon black content and crosslinking on the mechanical and electrical properties of a fluorinated elastomer, FC2178 (Dyneon Corp., Oakdale, MN), poly(vinylidene fluoride‐co‐hexafluoropropylene), were investigated and compared to those of poly(vinylidene fluoride) (PVDF). Attention was given to changes in mechanical and electrical properties of the polymers when under cyclic deformation. To describe the mechanical properties of the carbon‐filled polymers in a way that is independent of the chemical details, two mechanical models were used to fit cyclic stress–strain experiments. The linear model was used to determine the effect of crosslinking on the mechanical properties of crosslinked FC2178 films. However, when carbon black was added to the polymer films, the linear model no longer fit the data well. In particular, the cyclic stress–strain curves for carbon‐filled polymers showed non‐linear regions and displayed the characteristic of ‘memory.’ A non‐linear element was added in parallel with the existing elements of the linear model to successfully describe the effects of the added carbon black. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 1891–1899, 2003
Towards a national clinical minimum data set for general surgery
Authors: Prytherch D R , Sirl J S , Weaver P C , Schmidt P , Higgins B , Sutton G L
Published: September 2003

Background

Measurement and comparison of surgical performance is accepted as necessary and inevitable. Risk-stratified (case-mix adjusted) models of clinical outcomes form a metric with which to assess performance, but require accurate data. Collecting such data in the clinical environment is time consuming and difficult. This study aimed to construct effective models, for operative and non-operative admissions, from routine clinical data residing in hospital computers, so minimizing data collection and quality problems, and facilitating national implementation.

Methods

Data for 3181 non-operative emergency, 5039 elective and 3043 emergency operative admissions for the 2 years beginning 1 August 1997 were used to generate logistic regression equations for risk of death, which were applied prospectively to the following 3 years' data.

Results

The models use urea, haemoglobin, white blood cell count, sodium, potassium, age on admission, sex, British United Provident Association (BUPA) Operative Severity Score (for operative admissions) and, implicitly, mode of admission and mortality at discharge. All three models successfully stratified risk into five or more bands.

Conclusion

Effective models of mortality, applicable to all general surgical admissions, can be constructed from existing routine clinical data, largely obtained from a single venesection. The data set is a candidate national clinical minimum data set.
Differential dye coupling reveals lateral giant escape circuit in crayfish
Authors: Antonsen Brian L. , Edwards Donald H.
Published: September 2003

The lateral giant (LG) escape circuit of crayfish mediates a coordinated escape triggered by strong attack to the abdomen. The LG circuit is one of the best understood of small systems, but models of the circuit have mostly been limited to simple ball‐and‐stick representations, which ignore anatomical details of contacts between circuit elements. Many of the these contacts are electrical; here we use differential dye coupling, a technique which could help reveal connection patterns in many neural circuits, to reveal in detail the circuit within the terminal abdominal ganglion. Sensory input from the tailfan forms a somatotopic map on the projecting LG dendrites, which together with interafferent coupling mediates a lateral excitatory network that selectively amplifies strong, phasic, converging input to LG. Mechanosensory interneurons contact LG at sites distinct from the primary afferents and so maximize their summated effect on LG. Motor neurons and premotor interneurons are excited near the initial segments of the LGs and innervate muscles for generating uropod flaring and telson flexion. Previous research has shown that spatial patterns of input are important for signal integration in LG; this map of electrical contact points will help us to understand synaptic processing in this system. J. Comp. Neurol. 466:1–13, 2003. © 2003 Wiley‐Liss, Inc.
Functional CD25– and CD25+ mucosal regulatory T cells are induced in gut‐draining lymphoid tissue within 48 h after oral antigen application
Authors: Hauet‐Broere Femke , Unger Wendy W. J. , Garssen Johan , Hoijer Maarten A. , Kraal Georg , Samsom Janneke N.
Published: September 2003

Oral antigen application induces tolerance, leading to suppression of a subsequent systemic challenge with this antigen. The suppression is mediated by mucosal regulatory T (Tr) cells that maydifferentiate from naive peripheral T cells in the gut‐draining lymphoid tissue. However, little is known about the initial steps of this differentiation process. In this study we show that 48 h after oral OVA treatment, antigen‐specific T cells in mesenteric lymph nodes (MLN) and Peyer's Patches (PP) were activated and had divided up to four times. The first division was already seen in PP after 24 h. Analysis of surface marker expression and cytokine secretion of the dividing antigen‐specific T cells revealed that they sequentially obtained an activation‐ and memory‐like phenotype. These cells secreted IL‐2 in most stages of division but only transiently IFN‐γ whereas no IL‐4 or IL‐10 secretion was detected. Remarkably, 48 h after antigen application, isolated dividing cellswere suppressive, as they transferred tolerance to naive mice. Even though CD25 was expressed heterogeneously, both CD25+ and CD25– OVA‐specific T cells from MLN could transfer tolerance. Together these findings show that differentiation of functional Tr cells occurs in the MLN and PP within 2 days after antigen ingestion and involves the generation of CD25+ and CD25– antigen‐specific T cells.
Correction: The natural killer cell‐mediated killing of autologous dendritic cells is confined to a cellsubset expressing CD94/NKG2A, but lacking inhibitory killer Ig‐like receptors
Authors: Della Chiesa M. , Vitale M. , Carlomagno S. , Ferlazzo G. , Moretta L. , Moretta A.
Published: September 2003

Vol. 33(6) 2003, pp 1657‐1666

The surname of the first author is Della Chiesa; thus the running title in the manuscript should have been given as M. Della Chiesa et al.
Correction: Measurement and modeling of human T cell kinetics
Authors: Macallan D. C. , Asquith B. , Irvine A. J. , Wallace D. L. , Worth A. , Ghattas H. , Zhang Y. , Griffin G. E. , Tough D. F. , Beverley P. C.
Published: September 2003

Vol. 33(8) 2003, pp 2316‐2326

Page 2319

Unfortunately, the equation indicating the rate of change of labeled deoxyadenosine was printed incorrectly. This should read:
equation image

equation image

Where τ  is the length of the labeling period.

Solving analytically yields:
equation image
during the labeling period
equation image
after the labeling period.

(http://dx.doi.org/10.1002/eji.200323763)
Downsizing outcomes: Better a victim than a survivor?
Authors: Devine Kay , Reay Trish , Stainton Linda , Collins‐Nakai Ruth
Published: September 2003

Is it better to be laid off when a downsizing initiative is announced? We analyze the outcomes
experienced by both victims and survivors involved in a major downsizing program, and present a model of
downsizing stress. Results indicate that displaced employees, or “victims,” who secure new
employment fare better than survivors. The victims in our study perceive higher levels of control, less stress,
and fewer negative job strains than continuing workers, or “survivors.” These results lend credence
to suggestions that stress and control are critical factors in understanding employee reactions to downsizing.
© 2003 Wiley Periodicals, Inc.