bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

AbstractTrying 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.
Prime-boost strategies for malaria vaccine development
Authors: Dunachie Susanna J. , Hill Adrian V. S. 
Published: September 2003

SUMMARYMalaria 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

SUMMARYThe 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.
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.
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

AbstractThe 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

Abstract

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

AbstractThe 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

AbstractOral 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

AbstractVol. 33(6) 2003, pp 1657‐1666The 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

AbstractVol. 33(8) 2003, pp 2316‐2326Page 2319Unfortunately, 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

AbstractIs 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.
Rapid vegetation change during the early Holocene in the Faroe Islands detected in terrestrial and aquatic ecosystems
Authors: Hannon Gina E. , Bradshaw Richard H. W. , Wastegård Stefan 
Published: September 2003

AbstractHigh‐resolution pollen, plant macrofossil and sedimentary analyses from early Holocene lacustrine sediments on the Faroe Islands have detected a significant vegetation perturbation suggesting a rapid change in climate between ca. 10 380 cal. yr BP and the Saksunarvatn ash (10 240±60 cal. yr BP). This episode may be synchronous with the decline in δ18O values in the Greenland ice‐cores. It also correlates with a short, cold event detected in marine cores from the North Atlantic that has been ascribed to a weakening of thermohaline circulation associated with the sudden drainage of Lake Agassiz into the northwest Atlantic, or, alternatively, a period with distinctly decreased solar forcing.The vegetation sequence begins at ca. 10 500 cal. yr BP with a succession from tundra to shrub‐tundra and increasing lake productivity. Rapid population increases of aquatic plants suggest high summer temperatures between 10 450 and 10 380 cal. yr BP. High pollen percentages, concentrations and influx of Betula, Juniperus and Salix together with macrofossil leaves indicate shrub growth around the site during the initial phases of vegetation colonisation. Unstable conditions followed ca. 10 380 cal. yr BP that changed both the upland vegetation and the aquatic plant communities. A decrease in percentage values of shrub pollen is recorded, with replacement of both aquatics and herbaceous plants by pioneer plant communities. An increase in total pollen accumulation rates not seen in the concentration data suggests increased sediment delivery. The catchment changes are consistent with less seasonal, moister conditions. Subsequent climatic amelioration reinitiated a warmth‐driven succession and catchment stabilisation, but retained high precipitation levels influencing the composition of the post‐event communities. Copyright © 2003 John Wiley & Sons, Ltd.
Dating the introduction of cereal cultivation to the British Isles: early palaeoecological evidence from the Isle of Man
Authors: Innes James B. , Blackford Jeffrey J. , Davey Peter J. 
Published: September 2003

AbstractThe adoption of cereal cultivation is a key benchmark in the transition from Mesolithic hunter–gatherer foraging to Neolithic farming economies, but the nature, timing and ecological–cultural context of the earliest cereal use in the British Isles and northwest Europe is still uncertain. We present AMS radiocarbon dating and fine‐resolution pollen evidence from the Isle of Man for cereal growing in the latter stages of a distinct episode of forest disturbance at almost 6000 yr BP (uncalibrated). The coherent ecological structure of this phase at the fine resolution level suggests that it records cereal cultivation well before the Ulmus decline, rather than wild grass pollen grains. This example is one of a cluster of early dates for cereal‐type pollen near the start of the sixth millenium BP, including several around the Irish Sea, which indicate that the introduction of cereal agriculture probably occurred as early in the central British Isles as in the northern European plain. This early cereal phase is followed later by a probable phase of pre‐Ulmus decline pastoral activity. We also report Mesolithic age woodland disturbance around 7000 yr BP (uncalibrated) and the first radiocarbon dates for mid‐Holocene forest history of the Isle of Man. Copyright © 2003 John Wiley & Sons, Ltd.