bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigation of the mechanism of action of alemtuzumab in a human CD52 transgenic mouse model
Authors: Hu Yanping , Turner Michael J. , Shields Jacqueline , Gale Matthew S. , Hutto Elizabeth , Roberts Bruce L. , Siders William M. , Kaplan Johanne M. 
Published: May 2009

SummaryAlemtuzumab is a humanized monoclonal antibody against CD52, an antigen found on the surface of normal and malignant lymphocytes. It is approved for the treatment of B‐cell chronic lymphocytic leukaemia and is undergoing Phase III clinical trials for the treatment of multiple sclerosis. The exact mechanism by which alemtuzumab mediates its biological effects in vivo is not clearly defined and mechanism of action studies have been hampered by the lack of cross‐reactivity between human and mouse CD52. To address this issue, a transgenic mouse expressing human CD52 (hCD52) was created. Transgenic mice did not display any phenotypic abnormalities and were able to mount normal immune responses. The tissue distribution of hCD52 and the level of expression by various immune cell populations were comparable to those seen in humans. Treatment with alemtuzumab replicated the transient increase in serum cytokines and depletion of peripheral blood lymphocytes observed in humans. Lymphocyte depletion was not as profound in lymphoid organs, providing a possible explanation for the relatively low incidence of infection in alemtuzumab‐treated patients. Interestingly, both lymphocyte depletion and cytokine induction by alemtuzumab were largely independent of complement and appeared to be mediated by neutrophils and natural killer cells because removal of these populations with antibodies to Gr‐1 or asialo‐GM‐1, respectively, strongly inhibited the activity of alemtuzumab whereas removal of complement by treatment with cobra venom factor had no impact. The hCD52 transgenic mouse appears to be a useful model and has provided evidence for the previously uncharacterized involvement of neutrophils in the activity of alemtuzumab.
Antibodies to wounded tissue enhance cutaneous wound healing
Authors: Nishio Naomi , Ito Sachiko , Suzuki Haruhiko , Isobe Ken‐Ichi 
Published: May 2009

SummaryThe wound repair process is a highly ordered sequence of events that encompasses haemostasis, inflammatory cell infiltration, tissue regrowth and remodelling. Wound healing follows tissue destruction so we hypothesized that antibodies might bind to wounded tissues, which would facilitate the engulfment of damaged tissues by macrophages. Here, we show that B cells, which produce antibodies to damaged tissues, are engaged in the process of wound healing. Splenectomy delayed wound healing, and transfer of spleen cells into splenectomized mice recovered the delay in wound healing. Furthermore, wound healing in splenectomized nude mice was also delayed. Transfer of enriched B220+ cells by magnetic beads accelerated wound healing in splenectomized mice. We detected immunoglobulin G1 (IgG1) binding to wounded tissues by using fluorescein isothiocyanate‐labelled anti‐IgG1 6–24 hr after wounding. Splenectomy reduced the amount of IgG1 binding to wounded tissues. Immunoblotting studies revealed several bands, which were reduced by splenectomy. Using immunoprecipitation with anti‐IgG bound to protein G we found that the intensity of several bands was lower in the serum from splenectomized mice than in that from sham‐operated mice. These bands were matched to myosin IIA, carbamoyl‐phosphate synthase, argininosuccinate synthase, actin and α‐actinin‐4 by liquid chromatography tandem mass spectrometry analysis.
Single sequence repeat markers reflect diversity and geographic barriers in Eurasian populations of the conifer pathogen Ceratocystis polonica
Authors: Marin M. , Preisig O. , Wingfield B. D. , Kirisits T. , Wingfield M. J. 
Published: May 2009

SummaryThe blue‐stain fungus and vascular stain pathogen Ceratocystis polonica and its associated bark beetle vectors, particularly Ips typographus and I. typographus japonicus, cause significant losses to several spruce species in Eurasia. Nothing is, however, known about the population genetics of this conifer pathogen. In this study, a set of single sequence repeat (SSR) markers were developed to determine the population structure and genetic diversity of C. polonica in Europe and Japan. ISSR‐PCR primers were used to target SSR‐rich regions and specific primers were designed flanking the SSR regions found in these amplicons. The SSR primers developed for C. polonica were found to be transferable to six other Ceratocystis species from conifers, residing in the Ceratocystis coerulescens complex. Ninety‐eight isolates representing four populations of C. polonica (Austria, Norway, Poland and Japan) were tested using 10 selected polymorphic SSR markers. A high level of gene diversity was found in C. polonica as a whole (H = 0.53). Analysis of G statistics showed a low degree of population structure in Europe and a high level of gene flow between populations (Gst = 0.05, Nm = 8.5). In contrast, the Japanese and the European populations of C. polonica displayed strong genetic separation, which is likely caused by geographic isolation. The low level of population structure of C. polonica in Europe and the differentiation between the European and the Japanese fungal populations mirror previous findings for I. typographus and I. typographus japonicus, the main insect vectors of this fungus. These results support the view that the fungus and the insect have closely co‐evolved together. This study also suggests that movement of C. polonica and its vectors between Europe and Asia pose a threat to forestry on both continents and this should clearly be avoided.
Promoting mental health care in a rural paediatric unit through participatory action research
Authors: Happell Brenda , Moxham Lorna , Reid‐Searl Kerry , Dwyer Trudy , Kahl Julie , Morris Jodie , Wheatland Narelle 
Published: May 2009

AbstractObjective:  To explore, advance and evaluate mental health practices in a rural general paediatric unit through participatory action research. Design:  A participatory action research approach guided this study, providing an opportunity for nursing staff to become actively involved in the design, direction and outcomes of the research. Setting:  A 16‐bed paediatric unit of a rural general hospital. Participants:  A purposive convenience sample of all paediatric nursing staff (n = 20; of 24 nurses).Outcome measures:  In the first phase of this study, focus groups were conducted to explore the experiences of nurses. Results:  Participants considered mental health to be a specialist discipline area and the role of the mental health nurse to be complex. They felt that their lack of training and experience with mental health issues was detrimental to the delivery of optimal patient care. There was concern about differing approaches to treatment, relationships with other mental health services and the suitability of the ward environment for young people with a mental health problem. Participants called for training by qualified mental health staff and the development of policies and clinical guidelines to facilitate their delivery of care to patients with a mental health problem in an acute medical environment. Conclusions:  There is a clear need for nursing specialities to work together to ensure that optimal care is given to patients admitted to general hospital with a mental health issue. Given the absence of accessible specialist child mental health inpatient units in regional and remote areas, upskilling paediatric nurses must be a priority.
Landscape structure influences tree density patterns in fragmented woodlands in semi‐arid eastern Australia
Authors: DEBUSE VALERIE J. , HOUSE ALAN P. N. , TAYLOR DAVID W. , SWIFT SCOTT A. 
Published: May 2009

AbstractLandscape and local‐scale influences are important drivers of plant community structure. However, their relative contribution and the degree to which they interact remain unclear. We quantified the extent to which landscape structure, within‐patch habitat and their confounding effects determine post‐clearing tree densities and composition in agricultural landscapes in eastern subtropical Australia. Landscape structure (incorporating habitat fragmentation and loss) and within‐patch (site) features were quantified for 60 remnant patches of Eucalyptus populnea (Myrtaceae) woodland. Tree density and species for three ecological maturity classes (regeneration, early maturity, late maturity) and local site features were assessed in one 100 × 10 m plot per patch. All but one landscape characteristic was determined within a 1.3‐km radius of plots; Euclidean nearest neighbour distance was measured inside a 5‐km radius. Variation in tree density and composition for each maturity class was partitioned into independent landscape, independent site and joint effects of landscape and site features using redundancy analysis. Independent site effects explained more variation in regeneration density and composition than pure landscape effects; significant predictors were the proportion of early and late maturity trees at a site, rainfall and the associated interaction. Conversely, landscape structure explained greater variation in early and late maturity tree density and composition than site predictors. Area of remnant native vegetation within a landscape and patch characteristics (area, shape, edge contrast) were significant predictors of early maturity tree density. However, 31% of the explained variation in early mature tree differences represented confounding influences of landscape and local variables. We suggest that within‐patch characteristics are important in influencing semi‐arid woodland tree regeneration. However, independent and confounding effects of landscape structure resulting from previous vegetation clearing may have exerted a greater historical influence on older cohorts and should be accounted for when examining woodland dynamics across a broader range of environments.
High diversity Pleistocene rainforest Dasyurid assemblages with implications for the radiation of the dasyuridae
Authors: CRAMB JONATHAN , HOCKNULL SCOTT , WEBB GREGORY E. 
Published: May 2009

AbstractIt is commonly accepted that dasyurids (Marsupialia: Dasyuridae) radiated in the late Miocene or early Pliocene in response to a drying trend in Australia's climate as evidenced from the high diversity of dasyurids from modern arid environments compared with Miocene rainforest assemblages. However, mid‐Pleistocene dasyurid assemblages from cave deposits at Mt Etna, Queensland are more diverse than any previously known from rainforest habitats. New taxa will be described elsewhere, but include three new genera as well as new species of Dasyurus, Antechinus and Phascogale. Comparison of dasyurids from Mt Etna sites that are interpreted as rainforest palaeoenvironments with fossil and extant assemblages indicate that they are at least as diverse as those from modern arid environments. Thus Neogene diversification of dasyurids occurred in both arid and rainforest habitats, but only the former survived continuing aridification. Hence, aridification cannot be invoked for the diversification of all dasyurid lineages.
Environmental modulation of reproductive activity of the invasive mussel Limnoperna fortunei: implications for antifouling strategies
Authors: BOLTOVSKOY DEMETRIO , SYLVESTER FRANCISCO , OTAEGUI ALEJANDRO , LEITES VALENTÍN , CATALDO DANIEL H. 
Published: May 2009

Abstract Limnoperna fortunei (Dunker, 1857) (Bivalvia) invaded Argentina through the Río de la Plata estuary around 1990 and is presently established throughout five South American countries as a dominant component of the benthic fauna and a major nuisance for industry and power plants. Between 1997 and 2006 we monitored the reproductive activity of L. fortunei through weekly measurements of planktonic larvae in six South American water bodies: Río de la Plata estuary, Paraná and Carapachay rivers, Salto Grande, Itaipú and Embalse de Río Tercero reservoirs. Mean larval densities varied between 4000 and 7000 individuals m−3; except in the reservoirs of Itaipú (450 ind. m−3) and Salto Grande (869 ind. m−3), where the mussel was first recorded shortly before our surveys, and upstream dispersal is limited (Salto Grande). In all cases, reproductive output decreases during the winter. At four of the six sites surveyed larval densities were comparatively high for 8.8–10.2 months per year. A lower food supply is possibly responsible for the shorter reproductive period of 5.9 months at Embalse. At Salto Grande, there is a well‐defined mid‐summer drop in larval numbers, coinciding with blooms of cyanobacteria. We propose that, in addition to temperature, two major factors may regulate the reproductive activity of L. fortunei: (i) the availability of food; and (ii) blooms of toxic cyanobacteria, significantly shortening the otherwise very long reproductive period. This information is important for the design of antifouling programmes involving the use of molluscicides, and has potential for reduced biocide use. These results provide supporting evidence for some fundamental ecological theories of invasions discussed here.
Reproductive potential and seedling establishment of the invasive alien tree Schinus molle (Anacardiaceae) in South Africa
Authors: IPONGA DONALD M. , MILTON SUZANNE J. , RICHARDSON DAVID M. 
Published: May 2009

Abstract Schinus molle (Peruvian pepper tree) was introduced to South Africa more than 150 years ago and was widely planted, mainly along roads. Only in the last two decades has the species become naturalized and invasive in some parts of its new range, notably in semi‐arid savannas. Research is being undertaken to predict its potential for further invasion in South Africa. We studied production, dispersal and predation of seeds, seed banks, and seedling establishment in relation to land uses at three sites, namely ungrazed savanna once used as a military training ground; a savanna grazed by native game; and an ungrazed mine dump. We found that seed production and seed rain density of S. molle varied greatly between study sites, but was high at all sites (384 864–1 233 690 seeds per tree per year; 3877–9477 seeds per square metre per year). We found seeds dispersed to distances of up to 320 m from female trees, and most seeds were deposited within 50 m of putative source trees. Annual seed rain density below canopies of Acacia tortillis, the dominant native tree at all sites, was significantly lower in grazed savanna. The quality of seed rain was much reduced by endophagous predators. Seed survival in the soil was low, with no survival recorded beyond 1 year. Propagule pressure to drive the rate of recruitment: densities of seedlings and sapling densities were higher in ungrazed savanna and the ungrazed mine dump than in grazed savanna, as reflected by large numbers of young individuals, but adult : seedling ratios did not differ between savanna sites. Frequent and abundant seed production, together with effective dispersal of viable S. molle seed by birds to suitable establishment sites below trees of other species to overcome predation effects, facilitates invasion. Disturbance enhances invasion, probably by reducing competition from native plants.
Phase II study of paclitaxel and vinorelbine (Pacl‐Vin) in hormone‐refractory metastatic prostate cancer: double tubulin targeting
Authors: Sewak S. , Kosmider S. , Ganju V. , Woollett A. , Yeow E. G. , Le B. , Henry M. , Debrincat M. A. , Bell R. 
Published: May 2009

AbstractBackground: Androgen ablation is the standard treatment for advanced prostate cancer. However, most patients will eventually develop progressive hormone‐refractory prostate cancer (HRPC). The aim of the Pacl‐Vin study was to determine the efficacy and safety of paclitaxel in combination with vinorelbine in patients with HRPC, following from a phase I trial.Methods: Thirty castrate patients with progressive, metastatic prostate cancer were enrolled. Patients were treated with paclitaxel 40 mg/m2, vinorelbine 20 mg/m2 intravenously on day 1 and day 8 of a 21‐day cycle.Results: Two patients demonstrated a partial response and seven patients had stable disease from a cohort of 10 patients with measurable disease. Of 30 patients assessable for prostate‐specific antigen (PSA) response, 19 showed stable disease, which was maintained for at least 4 weeks, while six (20%) experienced ≥50% decline in PSA levels. Median overall survival was 7.3 months (interquartile range (IQR): 4.7–9.9 months). Median progression‐free survival was 3.3 months (IQR: 2.5–7.0 months). Improvement in quality of life measures was noted after three cycles of therapy. Grade 3 and 4 toxicities were: neutropenia 8%, febrile neutropenia 4%, infection 2%, anaemia 3%, lethargy 1% and somnolescence 1%. One patient died as a result of neutropenic sepsis.Conclusion: In a poor prognostic cohort of patients paclitaxel and vinorelbine is a tolerable regimen, with a 20% PSA and objective response rate. The majority of patients achieved PSA stability. Furthermore, quality of life parameters, such as pain, were improved. However, the low level of activity of this regimen precludes its further testing.
Growth hormone‐releasing peptide 6 protection of hypothalamic neurons from glutamate excitotoxicity is caspase independent and not mediated by insulin‐like growth factor I
Authors: Delgado‐Rubín A. , Chowen Julie A. , Argente Jesús , Frago Laura M. 
Published: May 2009

AbstractTreatment of the fetal hypothalamic neuronal cell line RCA‐6 with growth hormone‐releasing peptide 6, an agonist of the ghrelin receptor, or insulin‐like growth factor I activates intracellular signalling cascades associated with anti‐apoptotic actions. Abnormally high concentrations of glutamate provoke over‐excitation of neurons leading to cell damage and apoptosis. Thus, the aim of this study was to investigate whether the administration of growth hormone‐releasing peptide 6 and insulin‐like growth factor I attenuates monosodium glutamate‐induced apoptosis in RCA‐6 neurons and the mechanisms involved. Two different mechanisms are involved in glutamate‐induced cell death, one by means of caspase activation and the second through activation of a caspase‐independent pathway of apoptosis mediated by the translocation of apoptosis‐inducing factor. Growth hormone‐releasing peptide 6 partially reversed glutamate‐induced cell death but not the activation of caspases, suggesting blockage of the caspase‐independent cell death pathway, which included interference with the translocation of apoptosis‐inducing factor to the nucleus associated with the induction of Bcl‐2. In contrast, the addition of insulin‐like growth factor I to RCA‐6 neurons abolished glutamate‐induced caspase activation and cell death. These data demonstrate for the first time a neuroprotective role for growth hormone secretagogues in the caspase‐independent cell death pathway and indicate that these peptides have neuroprotective effects independent of its induction of insulin‐like growth factor I.
NR2A‐containing NMDA receptors are required for L‐LTP induction and depotentiation in CA1 region of hippocampal slices
Authors: Zhang Li , Meng Kai , Li Yan‐Hai , Han Tai‐Zhen 
Published: May 2009

AbstractLong‐term potentiation (LTP) is a well‐characterized form of synaptic plasticity that fulfills many of the criteria for the neural correlate of memory. LTP reversal (or depotentiation, DP) is thought to correlate with prevention or elimination of memory storage. LTP during and immediately after induction can be easily reversed by afferent stimulation, when applied within the optimal time window. The aim of the present study was to determine whether later‐phase LTP (L‐LTP) could be reversed by special patterned stimulation applied at 2 h after LTP induction, as well as to characterize the receptor mechanisms underlying this reversal. Field excitatory postsynaptic potentials evoked by Schaffer collateral stimulation were recorded from the CA1 subfield of adult rat hippocampal slices. Results demonstrated that stable LTP, which was induced by six theta‐burst stimulations, was mediated by NR2A‐containing N‐methyl‐d‐aspartate receptors (NMDARs). This L‐LTP was partially reversed by high‐intensity paired‐pulse low‐frequency stimulation (HI‐PP‐LFS) and was inhibited by Zn2+ (30 nm), a voltage‐independent NR2A‐NMDAR antagonist. However, NR2B‐NMDAR antagonists (Ro 25‐6981, 1 μm) displayed no effect on L‐LTP reversal. L‐LTP partial reversal was also induced by HI‐PP‐LFS, when the protein synthesis inhibitors anisomycin (25 μm) and cycloheximide (60 μm) were applied following LTP induction. These results suggested that NR2A‐containing NMDARs are required for L‐LTP induction and DP in the hippocampal CA1 area of adult rats. Moreover, HI‐PP‐LFS was an effective stimulation pattern to induce DP.
Glycaemic risk assessment in children and young people with Type 1 diabetes mellitus
Authors: Hill N. R. , Thompson B . , Bruce J. , Matthews D. R. , Hindmarsh P. 
Published: May 2009

AbstractAim  To ascertain if those with diabetes (and their carers) ascribe a similar level of risk to blood glucose control as healthcare professionals.Methods  We used a structured questionnaire to ask fifty healthcare professionals how ‘dangerous’ a given blood glucose value was. Their answers were modelled to produce an algorithm of assessed risk. To examine if patients (and their carers) would apportion a similar level of risk to that of healthcare professionals, the same questionnaire was issued to fifty children and adolescents with Type 1 diabetes. For patients under 8 years old the carers completed the questionnaires (n = 23). Both patient and carers together completed the questionnaire for those aged 8–11 years (n = 15) and patients over the age of 11 years completed the questionnaire themselves (n = 12). The median results and interquartile range of the assessed level of risk, as determined by the two groups, were compared using a generalized linear model.Results  A significant difference (P < 0.0001) was identified between the median risk assessments of the two groups. The zero level of assessed risk was upward shifted in the patient group by 0.8 mmol/l and indicated the patients’ view of risk increased.Conclusions  Patients with Type 1 diabetes (and their carers) evaluate the risk from blood glucose values differently from healthcare professionals. The euglycaemic state (zero ascribed risk) that patients chose was 0.8 mmol/l greater than that of healthcare professionals, indicating, perhaps, hypoglycaemia avoidance, a more pragmatic approach or less exposure to current trends in glycaemic control.