bluuebunny/crossref_metadata_2025_split huggingface dataset:
A new asthma spacer device to improve compliance in children: a pilot study
Authors: CHANEY Gervase , CLEMENTS Barry , LANDAU Lou , BULSARA Max , WATT Paul 
Published: December 2004

Objective:  This pilot study was designed to compare the acceptance, ease of use, and effects on compliance between currently used spacer devices and the Funhaler—a new small volume spacer device designed to improve adherence to asthma medication in children.Methodology:  A matched questionnaire‐based survey was conducted by two interviews of each caregiver by the same person. A total of 32 children were randomly recruited from seven clinics spanning widely differing socioeconomic and geographical areas of Perth, Western Australia. Preschool children taking regular inhaled asthma medication using an existing low volume spacer device and aged between 1.5 and 6 years, took part in the pilot study. Parents completed two matched questionnaires. The first questionnaire was completed at the beginning of the study and the second after 2 weeks’ use of the Funhaler spacer. Data collected related primarily to ease of use of the devices, child and parental compliance, and treatment attitudes. During the study, parents were also called at random on one occasion to ascertain whether they had attempted to medicate their child the previous day.Results:  Using the Funhaler incentive spacer device, parents reported significantly more success at medicating their children (22/30 always successful) in comparison to using their existing spacer device (3/30). Parental adherence to prescribed frequency and the delivery technique of children were also improved. The children also showed improved satisfaction and willingness to use the device and parents’ attitude towards medicating their children was improved with the Funhaler spacer device.Conclusions:  Use of a novel, incentive spacer device (Funhaler) appeared to be associated with increased success and fewer problems in medicating children, improved child and parental adherence, and a more positive attitude towards treatment, suggesting that more extensive long‐term efficacy trials with the device are warranted.
Glutathione‐S‐transferase gene polymorphisms (GSTT1, GSTM1, GSTP1) as increased risk factors for asthma
Authors: TAMER Lülüfer , ÇALIKOĞLU Mukadder , ATES Nurcan Aras , YILDIRIM Hatice , ERCAN Bahadir , SARITAS Emel , ÜNLÜ Ali , ATIK Ugur 
Published: December 2004

Objectives:  Asthma is a complex multifactorial disease with an obvious genetic predisposition, immunological aberration, and involvement of noxious environmental factors. Polymorphisms of the glutathione‐S‐transferase (GST) genes are known risk factors for some environmentally‐related diseases. In the present study, the hypothesis that polymorphisms in the GSTT1, GSTM1 and GSTP1 genes are associated with atopic and nonatopic asthma was examined.Methodology:  The study population consisted of 103 unrelated healthy individuals and 101 patients with bronchial asthma (64 atopic, 37 nonatopic). Asthma was diagnosed according to the American Thoracic Society statement. Genotyping of polymorphisms in the GSTT1, GSTM1 and GSTP1 genes was performed using real time polymerase chain reaction with a Light Cycler instrument and hybridization probes in combination with the Light Cycler DNA master hybridization probes kit.Results:  Patients with atopic asthma (34.4%) had a higher prevalence of the GSTT1 null genotype than the nonatopic asthma patients (13.5%; OR = 3.83; 95% CI, 1.24–11.78). Asthma patients (63.4%) had a higher prevalence of the GSTM1 null genotype than the control group (40.8%; OR = 2.34; 95% CI, 1.31–4.20). Subjects with the GSTP1 homozygous Val/Val genotype had a 3.55‐fold increased risk of having atopic asthma compared to nonatopic asthma (OR = 3.55; 95% CI, 1.10–12.56).Conclusions:  These results suggest that the GSTT1 and GSTM1 null genotypes and the GSTP1 Val/Val polymorphism may play important roles in asthma pathogenesis. It is possible that intermediate electrophilic metabolites, arising in the first phase of detoxification, are not metabolized by GST enzymes in asthmatic patients and are not excreted. These intermediate metabolites may damage cells and generate oxidative stress, and so contribute to the pathogenesis of asthma.
Augmentation mammoplasty and ‘silicone‐osis’
Authors: Englert H. , Joyner E. , Thompson M. , Garcia H. , Chambers P. , Horner D. , Hunt C. , Makaroff J. , O'Connor H. , Russell N. , March L. 
Published: December 2004

AbstractBackground: Claims have been made that breast augmentation induces a previously unrecognized disease (‘silicone‐osis’).Aims: To confirm the existence of ‘silicone‐osis’, qualify and quantify its characteristics.Methods: In this population‐based retrospective cohort study, the health status of 458 female Sydney residents who had augmentation mammoplasty for cosmetic reasons (‘augmentation mammoplasty‐exposed’ or ‘exposed’ cohort) between 1979 and 1983 was compared with the health status of 687 female Sydney residents who had non‐silicone‐associated plastic surgery (‘augmentation mammoplasty‐nonexposed’ or ‘non‐exposed’ cohort). Both groups were matched for age (± 5 years), year of plastic surgery (± 2 years), plastic surgeon, anaesthetist and mode of anaesthesia. Outcome measures comprised dummy symptoms to assess reporting bias, as well as symptoms and symptom clusters from a comprehensive 78‐symptom list.Results: Dummy variables were not over‐reported by the exposed cohort. The following individual symptoms developed more commonly in the exposed cohort after index plastic surgery: ‘memory loss/confusion’, ‘altered bowel habit’, ‘chest pain made worse by deep breathing’, ‘shortness of breath after walking up 10 steps’‘breast pain’, ‘sweating mainly at night’ and ‘tunnel vision’. Of eight identified symptom clusters, three were rejected as biologically unimportant: ‘joint swelling of the bunion joint’, ‘haemorrhoids’ and ‘breast lumps’ (the latter two occurring more commonly in the non‐exposed cohort). In contrast, five symptom clusters were thought to have potential biological importance and occurred more commonly in the exposed cohort. The symptom ‘night sweats’ was common to all five clusters, and comprised the sole symptom in one instance. The other four multisymptom clusters were also characterized by ‘low energy’ (lethargy) and ‘pins and needles’, whereas ‘breast pain’, ‘impaired memory’, ‘muscle pain’ and ‘reflux’, occurred in three of the four clusters.Conclusion: Cluster analysis suggested the existence of a multisystem disorder occurring more commonly in the exposed cohort and characterized by night sweats, lethargy, breast pain, impaired mentation, reflux, paraesthesiae, hand muscle weakness and myalgia. The argument against this being a new disease entity −‘silicone‐osis’− however, was its presence, albeit at lower frequency, in the silicone‐unexposed cohort. Thus this study did not confirm the existence of a new disease entity ‘silicone‐osis’ uniquely and causally associated with silicone exposure. The possible interpretations of these findings are discussed. (Intern Med J 2004; 34: 668−676)
Tumour necrosis factor inhibitors: risks and benefits in patients with rheumatoid arthritis
Authors: Roberts L. , McColl G. J. 
Published: December 2004

AbstractRheumatoid arthritis (RA) is the most common form of inflammatory arthritis and can, if left untreated, result in significant disability and early death. It is also associated with large direct and indirect costs to the individual and to society. Early and aggressive disease modifying anti‐rheumatic drug (DMARD) treatment of patients at risk of erosive disease has improved the outcome in the majority, but not all, RA patients. Tumour necrosis factor (TNF) appears to be a key mediator of the inflammatory and destructive process in RA, and consequently inhibitors of TNF action have been tested in randomized controlled trials in patients with RA. The results of these studies have suggested that TNF inhibitors are potent DMARD particularly when combined with methotrexate. They appear well tolerated with the commonest adverse events related to their parenteral route of administration, and the serious but rare side‐effects being various infections, notably tuberculosis, multiple sclerosis, and worsening of cardiac failure. Treatment costs are high and range from $15 000 to $25 000 per patient per year. Etanercept, adalimumab and infliximab have recently been subsidised under the Pharmaceutical Benefits Scheme in Australia for patients with severe DMARD‐resistant RA. The availability of TNF inhibitors in RA represents a significant advance in the treatment of patients with severe RA. (Intern Med J 2004; 34: 687−693)
Using marine reserves to estimate fishing mortality
Authors: Willis Trevor J. , Millar Russell B. 
Published: December 2004

AbstractThe proportion of a fish stock that is killed by fishing activity is often calculated as the catch divided by the estimated stock biomass. However, stock biomass is notoriously difficult to estimate reliably, and moreover, the catch may be uncertain or misreported and does not include losses due to discarding. In all too many fisheries, these difficulties have lead to underestimates of total fishing mortality and the commercial demise of the fishery. No‐take marine reserves eliminate fishing mortality from within their boundaries and, for species that exhibit seasonal migratory behaviour, comparison of reserves with fished areas can provide direct estimates of the proportion killed by fishing. For an important exploited species in New Zealand, seasonal changes in density of sub‐legal fish at three marine reserves were similar in both reserve and adjacent non‐reserve areas. However, this result did not hold for legal‐size fish, and the difference in seasonal change between reserved and non‐reserved areas was used to obtain direct estimates of the total localized fishing mortality in the non‐reserve area over 6‐month periods. Estimates of the percentage of legal‐size fish killed by fishing ranged from 70 to 96%. These results demonstrate an unanticipated practical benefit from marine reserves that goes beyond their ecological role.
Bacterial traits, organism mass, and numerical abundance in the detrital soil food web of Dutch agricultural grasslands
Authors: Mulder Christian , Cohen Joel E. , Setälä Heikki , Bloem Jaap , Breure Anton M. 
Published: December 2004

AbstractThis paper compares responses to environmental stress of the ecophysiological traits of organisms in the detrital soil food webs of grasslands in the Netherlands, using the relationship between average body massMand numerical abundanceN. The microbial biomass and biodiversity of belowground fauna were measured in 110 grasslands on sand, 85 of them farmed under organic, conventional and intensive management. Bacterial cell volume and abundance and electrophoretic DNA bands as well as bacterial activity in the form of either metabolic quotient (qCO2) or microbial quotient (Cmic/Corg) predicted the response of microorganisms to stress. For soil fauna, the logarithm of body mass log(M) was approximately linearly related to the logarithm of numerical abundance log(N) with slope near −1, and the regression slope and the proportion of predatory species were lower in intensive agroecosystems (more reduced substrates with higher energy content). Linear regression of log(N) on log(M) had slope not far from −3/4. The approach to monitoring data illustrated in this paper could be useful in assessing land‐use quality.
A Panel Data Analysis of the Effects of Wages, Standard Hours and Unionization on Paid Overtime Work in Britain
Authors: Kalwij Adriaan S. , Gregory Mary 
Published: December 2004

SummaryThis study examines the effects of the basic wage rate, standard working hours and unionization on paid overtime work in Britain by using individual level data from the New Earnings Survey over the period 1975–2001. For this purpose we estimate a panel data model. We show that to obtain consistent estimates it is important to allow for both the censoring of paid overtime hours at 0 and for correlations between the explanatory variables and unobserved individual-specific effects. The main empirical results are that a reduction in standard hours increases both the incidence of overtime and overtime hours, whereas an increase in the wage rate decreases the incidence of overtime but brings a small increase in overtime hours for those working overtime. For men the effects are stronger than for women. Union coverage is of minor empirical importance. The occupation and industry structure of employment has shifted from high to lower overtime jobs. Taken together, these economic variables can explain almost half of the changing incidence of overtime for men, and most of the change in overtime hours worked by women, but are less successful in explaining the changes in overtime hours worked by men or the incidence of overtime for women.
The Cytoplasmic Tail Slows the Folding of Human Immunodeficiency Virus Type 1 Env from a Late Prebundle Configuration into the Six-Helix Bundle
Authors: Abrahamyan Levon G. , Mkrtchyan Samvel R. , Binley James , Lu Min , Melikyan Grigory B. , Cohen Fredric S. 
Published: December 2004

ABSTRACT
Effects of the cytoplasmic tail (CT) of human immunodeficiency virus type 1 Env on the process of membrane fusion were investigated. Full-length Env (wild type [WT]) and Env with its CT truncated (ΔCT) were expressed on cell surfaces, these cells were fused to target cells, and the inhibition of fusion by peptides that prevent Env from folding into a six-helix bundle conformation was measured. For both X4-tropic and R5-tropic Env proteins, ΔCT induced faster fusion kinetics than did the WT, and peptides were less effective at inhibiting ΔCT-induced fusion. We tested the hypothesis that the inhibitory peptides were less effective at inhibiting ΔCT-induced fusion because ΔCT folds more quickly into a six-helix bundle. Early and late intermediates of WT- and ΔCT-induced fusion were captured, and the ability of peptides to block fusion when added at the intermediate stages was quantified. When added at the early intermediate, the peptides were still less effective at inhibiting ΔCT-induced fusion but they were equally effective at preventing WT- and ΔCT-induced fusion when added at the late intermediate. We conclude that for both X4-tropic and R5-tropic Env proteins, the CT facilitates conformational changes that allow the trimeric coiled coil of prebundles to become optimally exposed. But once Env does favorably expose its coiled coil to inhibitory peptides, the CT hinders subsequent folding into a six-helix bundle. Because of this facilitation of maximal exposure and hindrance of bundle formation, the coiled coil is optimally exposed for a longer time for WT than for ΔCT. This accounts for the greater peptide inhibition of WT-induced fusion.
Macrophages Kill Human Papillomavirus Type 16 E6-Expressing Tumor Cells by Tumor Necrosis Factor Alpha- and Nitric Oxide-Dependent Mechanisms
Authors: Routes John M. , Morris Kristin , Ellison Misoo C. , Ryan Sharon 
Published: December 2004

ABSTRACTThe expression of adenovirus serotype 2 or 5 (Ad2/5) E1A sensitizes cells to killing by NK cells and activated macrophages, a property that correlates with the ability of E1A to bind the transcriptional coadaptor proteins p300-CBP. The E6 oncoproteins derived from the high-risk human papillomaviruses (HPV) interact with p300 and can complement mutant forms of E1A that cannot interact with p300 to induce cellular immortalization. Therefore, we determined if HPV type 16 (HPV16) E6 could sensitize cells to killing by macrophages and NK cells. HPV16 E6 expression sensitized human (H4 and C33A) and murine (MCA-102) cell lines to lysis by macrophages but not by NK cells. The lysis of cells that expressed E6 by macrophages was p53 independent but dependent on the production of tumor necrosis factor alpha (TNF-α) or nitric oxide (NO) by macrophages. Unlike cytolysis assays with macrophages, E6 expression did not significantly sensitize cells to lysis by the direct addition of NO or TNF-α. Like E1A, E6 has been reported to sensitize cells to lysis by TNF-α by inhibiting the TNF-α-induced activation of NF-κB. We found that E1A, but not E6, blocked the TNF-α-induced activation of NF-κB, an activity that correlated with E1A-p300 binding. In summary, Ad5 E1A and HPV16 E6 sensitized cells to lysis by macrophages. Unlike E1A, E6 did not block the ability of TNF-α to activate NF-κB or sensitize cells to lysis by NK cells, TNF-α, or NO. Thus, there appears to be a spectrum of common and unique biological activities that result as a consequence of the interaction of E6 or E1A with p300-CBP.
Role of Tumor Necrosis Factor Receptors in Regulating CD8 T-Cell Responses during Acute Lymphocytic Choriomeningitis Virus Infection
Authors: Suresh M. , Singh Anju , Fischer Christopher 
Published: December 2004

ABSTRACTThe role of tumor necrosis factor (TNF) in regulating various phases of the antiviral T-cell response is incompletely understood. Additionally, despite strong evidence ascribing a role for TNF in protecting against T-cell-dependent autoimmunity, the underlying mechanisms are still obscure. To address these issues, we have investigated the role of tumor necrosis factor receptors (TNFRs) I (p55R) and II (p75R) in regulating CD8 T-cell responses to lymphocytic choriomeningitis virus (LCMV) with wild-type, p55R-deficient (p55−/−), p75R-deficient (p75−/−), and p55R- and p75R-deficient (DKO) mice. Loss of p55R increased the number of memory CD8 T cells to only one of the two immunodominant epitopes, and p75R deficiency had a minimal impact on the T-cell response to LCMV. Strikingly, deficiency of both p55R and p75R had a more dramatic effect on the LCMV-specific CD8 T-cell response; in the DKO mice, as a sequel to enhanced expansion and a reduction in contraction of CD8 T cells, there was a substantial increase in the number of memory CD8 T cells (specific to the two immunodominant epitopes). While the majority of LCMV-specific memory CD8 T cells in wild-type mice were CD62LhiCCR7hi(central memory), a major proportion of memory CD8 T cells in DKO mice were CD62LloCCR7hi. TNFR deficiency did not affect the proliferative renewal of memory CD8 T cells. Taken together, these data suggested that TNFRs p55R and p75R have overlapping roles in downregulating CD8 T-cell responses and establishment of immune homeostasis during an acute viral infection.
La Crosse Virus Nonstructural Protein NSs Counteracts the Effects of Short Interfering RNA
Authors: Soldan Samantha S. , Plassmeyer Matthew L. , Matukonis Meghan K. , González-Scarano Francisco 
Published: December 2004

ABSTRACT
Through a process known as RNA interference (RNAi), double-stranded short interfering RNAs (siRNAs) silence gene expression in a sequence-specific manner. Recently, several viral proteins, including the nonstructural protein NSs of tomato spotted wilt virus (a plant-infecting bunyavirus), the interferon antagonist protein NS1 of influenza virus, and the E3L protein of vaccinia virus, have been shown to function as suppressors of RNAi, presumably as a counterdefense against cellular mechanisms that decrease viral production. La Crosse virus (LACV), a member of the California serogroup of orthobunyaviruses, has a trisegmented negative-stranded genome comprised of large (L), medium (M), and small (S) segments. To develop a strategy for segment-specific inhibition of transcription, we designed 13 synthetic siRNAs targeting specific RNA segments of the LACV genome that decreased LACV replication and antigen expression in mammalian (293T) and insect (C6/36) cells. Furthermore, NSs, a LACV nonstructural protein, markedly inhibited RNAi directed both against an LACV M segment construct and against a host gene (glyeraldehyde-3-phosphate dehydrogenase), suggesting a possible role for this viral protein in the suppression of RNA silencing. Segment-specific siRNAs will be useful as a tool to analyze LACV transcription and replication and to obtain recombinant viruses. Additionally, NSs will help us to identify molecular pathways involved in RNAi and further define its role in the innate immune system.
Human Endothelial Cells Enhance Human Immunodeficiency Virus Type 1 Replication in CD4+T Cells in a Nef-Dependent Manner In Vitro and In Vivo
Authors: Choi Jaehyuk , Walker Jason , Boichuk Sergei , Kirkiles-Smith Nancy , Torpey Nicholas , Pober Jordan S. , Alexander Louis 
Published: December 2004

ABSTRACTInfected CD4+T cells are the primary sites of human immunodeficiency virus type 1 (HIV-1) replication in vivo. However, signals from professional antigen-presenting cells (APCs), such as dendritic cells and macrophages, greatly enhance HIV-1 replication in T cells. Here, we report that in cocultures, vascular endothelial cells (ECs), which in humans can also serve as APCs, can enhance HIV-1 production of both CCR5- and CXCR4-utilizing strains approximately 50,000-fold. The observed HIV-1 replication enhancement conferred by ECs occurred only in memory CD4+T cells, required expression of major histocompatibility complex class II (MHC-II) molecules by the ECs, and could not be conferred by fixed ECs, all of which are consistent with a requirement for EC-mediated T-cell activation via T-cell receptor (TCR) signaling. Deletion ofnef(Nef−) decreased HIV-1 production by approximately 100-fold in T cells cocultured with ECs but had no effect on virus production in T cells cocultured with professional APCs or fibroblasts induced to express MHC-II. Human ECs do not express B7 costimulators, but Nef−replication in CD4+-T-cell and EC cocultures could not be rescued by anti-CD28 antibody. ECs act intransto enhance wild-type but not Nef−replication and facilitate enhanced wild-type replication in naïve T cells when added to T-cell or B-lymphoblastoid cell cocultures, suggesting that ECs also provide a TCR-independent signal to infected T cells. Consistent with these in vitro observations, wild-type HIV-1 replicated 30- to 50-fold more than Nef−in human T cells infiltrating allogeneic human skin grafts on human huPBL-SCID/bg mice, an in vivo model of T-cell activation by ECs. Our studies suggest that ECs, which line the entire cardiovascular system and are, per force, in frequent contact with memory CD4+T cells, provide signals to HIV-1-infected CD4+T cells to greatly enhance HIV-1 production in a Nef-dependent manner, a mechanism that could contribute to the development of AIDS.