bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fostering communication and shared play between mainstream peers and children with autism: approaches, outcomes and experiences
Authors: Whitaker Philip 
Published: December 2004

More pupils with autism are now being educated in mainstream settings and inevitably there is increased interest in their interactions with their peers. In this article, Philip Whitaker, of the Educational Psychology Service in Northamptonshire, describes his study of shared play between children with autism and their mainstream peers. The study involved ten youngsters with severe autism, educated in a unit attached to a mainstream school, and a group of volunteer ‘peer tutors’. The children met in weekly interaction sessions designed to promote shared play and communication. The peer tutors were provided with some coaching in interaction techniques and the impact of the intervention was evaluated through analysis of video recordings of play sessions made at the beginning and end of the project. The peer tutors and their parents were also interviewed at the end of the project to explore their experiences.The results Philip Whitaker reports are encouraging. All parents were strongly supportive of their children's participation. All but one of the peer tutors found the experience challenging but rewarding and wanted to continue their involvement beyond the 20‐week project. The video evidence revealed that the peer tutors, with relatively limited preparation, were able to engage the youngsters with autism in high and sustained levels of shared play. The frequency of requesting by children with autism increased substantially over the course of the project, although levels of initiation of shared attention remained consistently low. Philip Whitaker concludes his report with a series of suggestions for enhancing the impact of this interesting work.
Retrospective population pharmacokinetics of levocetirizine in atopic children receiving cetirizine: the ETAC® study
Authors: Hussein Ziad , Pitsiu Maria , Majid Oneeb , Aarons Leon , De Longueville Marc , Stockis Armel ,   the ETAC Study Group
Published: December 2004

AimsTo evaluate the population pharmacokinetics of levocetirizine in young children receiving long‐term treatment with cetirizine.MethodsData were available from a randomized, double‐blind, parallel group and placebo‐controlled study of cetirizine in 343 young children between 12 and 24 months of age at entry, who were at high risk of developing asthma, but were not yet affected (ETAC® study). Infants received oral drops of cetirizine at 0.25 mg kg−1 twice daily for 18 months. Plasma concentration of the active enantiomer levocetirizine was determined in blood samples collected at months 3, 12 and 18 (1–3 samples per child). A one‐compartment open model was fitted to the data using nonlinear mixed effects modelling (NONMEM). The influence of weight, age, gender, BSA and other covariates on CL/F and V/F was evaluated.ResultsCL/F increased linearly with weight by 0.044 l h−1 kg−1 over an intercept of 0.244 l h−1, and V/F increased linearly with weight by 0.639 l kg−1. Population estimates in children with weights of 8 and 20 kg were 0.60 and 1.13 l h−1 for CL/F, and 5.1 and 12.8 l for V/F, respectively, with interpatient variabilities of 24.4% and 14.7%. Weight‐normalized estimates of CL/F and V/F were higher than in adults. The estimated relative bioavailability was 0.28 in 12% of instances of suspected noncompliance. Levocetirizine pharmacokinetics were not influenced by severe allergy or aeroallergen sensitization. Results on the effects of concomitant medications or diseases were inconclusive due to limited positive cases. AUCss, calculated in compliant subjects using posterior estimates of the final model, was 1952 (1227–3319) µg l−1 h (mean, min‐max), a value similar to that in adults after intake of 5 mg oral solution (2036 (1414–2827) µg l−1 h.ConclusionsThe model suggests that administration of levocetirizine 0.125 mg kg−1 twice daily in children 12–48 months of age or weighing 8–20 kg yields the same exposure as in adults taking the recommended dose of 5 mg once daily.
A meta‐analysis of clinical trials of paclitaxel‐ and sirolimus‐eluting stents in patients with obstructive coronary artery disease
Authors: Shafiq N. , Malhotra S. , Pandhi P. , Grover A. , Uboweja A. 
Published: December 2004

AimThis meta‐analysis was conducted to compare the effects of drug (paclitaxel and sirolimus)‐eluting stents with bare metal stents on major adverse cardiac events, restenosis rates and late loss of arterial lumen diameter in patients with obstructive coronary artery disease.MethodsRandomized, controlled clinical trials comparing sirolimus‐ and paclitaxel‐eluting stents with bare metal stents were identified through electronic and manual search. Fixed effects method of Mantel‐Haenszel and random effects method of DerSimonian and Laird were used for computing the pooled odds ratio (OR) and 95% confidence intervals (CI) for major adverse cardiac events and restenosis rates. Standardized mean difference with 95% CI was calculated for late‐loss of arterial lumen diameter.ResultsA total of 13 studies were included in the meta‐analysis. As compared with bare metal stents, the use of sirolimus‐ and paclitaxel‐eluting stents significantly reduced the major adverse cardiac events (pooled OR 0.35; 95% CI 0.24–0.50), restenosis rates (pooled OR 0.27; 95% CI 0.15–0.47), and late loss of arterial lumen diameter (mean difference 0.57 mm, 95% CI 0.49–0.68).ConclusionPaclitaxel‐ and sirolimus‐eluting stents significantly reduced the incidence of major adverse cardiac events, restenosis rates, and late loss of arterial lumen diameter as compared with bare metal stents.
The effect of sepsis upon gentamicin pharmacokinetics in neonates
Authors: Lingvall M. , Reith D. , Broadbent R. 
Published: December 2004

AimTo investigate the effect of sepsis upon the volume of distribution (Vd) of gentamicin in neonates.MethodsA retrospective chart review was conducted of neonates admitted to Dunedin Hospital who had gentamicin concentrations performed between 1st January 2000 and 30th October 2003. Data from 277 neonates, including a total of 576 gentamicin concentrations, were included in the pharmacokinetic analysis. Fifteen (5.4%) of the neonates had confirmed sepsis. Pharmacokinetic analyses were performed with NONMEM using a one compartment first order elimination model. Duration of infusion (D) was included as a parameter in the model. Covariates included sepsis (SEP), chronological age, gestational age (GA), birth weight, current weight, gender, Apgar score at 1 (AP1) and 5 (AP2) minutes, plasma C‐reactive protein and serum creatinine.ResultsThe initial model provided a mean estimates of clearance (CL) of 0.0460 l kg−1 h−1, volume of distribution (Vd) of 0.483 l kg−1 and D of 0.748 h. The magnitudes of interpatient variability, expressed as CV%, were 29.2% for CL, 20.8% for Vd and 71.5% for D. The magnitude of residual variability in gentamicin concentrations was 88.0%. The final pharmacokinetic model was: CL = (0.0177 + 0.00147 • (GA‐20) + 0.000635 • AP2) l kg−1 h−1, Vd = (0.483 +0.0656 • sepsis) l kg−1, D = 0.672 h. The interpatient variability (CV%) was 22.8% for CL, 22.8% for Vd and 97.7% for D. The magnitude of residual variability in gentamicin concentrations was 83.3%.ConclusionsThe 14% increase in Vd in septic neonates implies that larger doses may be required to achieve peak therapeutic concentrations in the presence of sepsis. D is an important parameter in neonatal pharmacokinetic models.
Phenotypic and functional heterogeneity of porcine blood monocytes and its relation with maturation
Authors: Chamorro Sonia , Revilla Concepción , Álvarez Belén , Alonso Fernando , Ezquerra Ángel , Domínguez Javier 
Published: December 2004

SummarySwine monocytes constitute a heterogeneous population of cells which can be divided into four subsets based on the expression of SWC3, CD14, CD163 and swine leucocyte antigen (SLA) DR markers. These subsets appear to represent different maturation stages in a pathway along which these cells up‐regulate the expression of SLA DR and CD163 antigens and reduce that of CD14. Differences in the expression of adhesion and costimulatory molecules are also patent, with a progressive increase in the expression of CD11a, wCD11R1, CD29, CD49d, CD61, CD1a and CD80/86, and a concomitant decrease in that of wCD11R2. Besides, these subsets differ in their capacity for tumour necrosis factor‐α (TNF‐α) production in response to lipopolysaccharide + interferon‐γ. The CD163+ CD14− SLA DR+ subset produces higher amounts of TNF‐α than the CD163− CD14+ SLA DR− subset, whereas CD163+ CD14+ SLA DR+ and CD163− CD14+ SLA DR+ subsets show intermediate values. CD163+ monocytes also display a higher ability to present soluble antigens to T cells than CD163− monocytes.
No mixing of granulocytes and other lymphocytes in the inflamed joints of parabiosis mice with collagen‐induced arthritis: possible in situ generation
Authors: Nishizawa Tetsuro , Kawamura Toshihiko , Izumi Nakao , Kawamura Hiroki , Fujii Katsuyuki , Abo Toru 
Published: December 2004

SummaryCollagen‐induced arthritis was evoked by an injection of lipopolysaccharide and anti‐type II collagen antibody in mice. In parallel with the onset of arthritis, granulocytes with large light scatter and a Mac‐1+ Gr‐1+ phenotype expanded in the joints of these mice. Lymphocytes with a CD3− B220+ phenotype (i.e. B220+ B cells) were the major population among lymphocyte subsets in the joints, irrespective of disease. To determine the origin of these leucocyte populations in the joints and other organs, parabiotic experiments using CBF1Ly5.1 and CBF1Ly5.2 mice were conducted in mice with and without collagen‐induced arthritis. As expected, leucocyte populations in the liver and spleen became a half‐and‐half mixture of their own cells and partner cells (e.g. ∼45% of Ly5.1+ cells in Ly5.2+ partner mice). However, such a mixture was extremely delayed in the joints and bone marrow, even in mice with arthritis. These results suggest that, because circulatory blood is not exchanged in the joints, granulocytes and other lymphocytes are generated in situ in the inflamed joints of mice with collagen‐induced arthritis or are possibly supplied by the bone marrow. It is of interest that granulocytes in the joints expanded, even without a supply from another site, namely, the synovium.
Porin of Shigella dysenteriae enhances Toll‐like receptors 2 and 6 of mouse peritoneal B‐2 cells and induces the expression of immunoglobulin M, immunoglobulin G2a and immunoglobulin A
Authors: Ray Avijit , Biswas Tapas 
Published: December 2004

SummaryPorin of Shigella dysenteriae type 1 increased the mRNA levels for Toll‐like receptors TLR2 and TLR6, by 1·8‐fold and twofold, respectively, in peritoneal cavity B‐2 cells from C57BL/6 mice, implicating that the co‐expression of TLR2 and TLR6 occurs as a combinatorial repertoire in response to porin. Among the two key TLRs, TLR2 and TLR4, which are primarily responsible for recognizing the majority of bacterial products, TLR2 alone participates in porin recognition. TLR2 expression was increased on B‐2 cells, whereas the expression of TLR4 remained unaffected. Besides TLRs, mRNA for myeloid differentiation factor 88 (MyD88), an effector molecule associated with the TLR‐mediated response, was enhanced by twofold, suggesting its involvement in the activity of porin. The B‐2 cells showed a 1·8‐fold increase in mRNA expression of the signalling molecule, nuclear factor‐kappa B (NF‐κB), in the presence of porin. Porin treatment of B‐2 cells selectively up‐regulated the expression of the costimulatory molecule, CD86, by 4·4‐fold. Porin induced the cell‐surface expression of immunoglobulin (Ig)M, of IgG2a preferentially among the IgG subclasses, and of IgA, on B‐2 cells. The porin‐mediated inductions of IgG2a and IgA were augmented by interleukin‐6 on B‐2 cells, by 2·7‐ and 1·6‐fold, respectively.
Memory CD8+ T cells require CD8 coreceptor engagement for calcium mobilization and proliferation, but not cytokine production
Authors: Kerry Samantha E. , Maile Robert , Collins Edward J. , Frelinger Jeffrey A. 
Published: December 2004

SummaryMemory T‐cell responses are faster and more robust than those of their naïve counterparts. The mechanisms by which memory T cells respond better to subsequent antigenic exposure remain unresolved. A portion of the more rapid response is undoubtedly the result of the increased frequency of antigen‐specific cells. In addition, there are also differences in the cells themselves with respect to their requirements for costimulation and the apparent avidity of the T cells. We used major histocompatibility complex (MHC) class I tetramers to stimulate T cells to focus on the interaction of T‐cell receptor (TCR)/MHC and CD8 in the absence of other molecules that are present on cell surfaces and so contribute to the activation of T cells by undefined mechanisms. Mutated MHC class I tetramers that are unable to engage CD8 were used to investigate the role of CD8 engagement in memory cell activation. Either wild‐type tetramers or tetramers carrying the mutation were used to stimulate both memory and naïve TCR transgenic T cells in vitro. Surprisingly, like naïve cells, memory CD8+ T cells required CD8 engagement for calcium mobilization and optimum proliferation. In contrast, the requirements for cytokine production differed. Unlike naive cells, memory cells were able to produce cytokine in the absence of CD8 engagement. This suggests both a CD8‐dependent pathway for early events and a CD8‐independent pathway for cytokine production in memory cells.
A transcriptional regulatory element in the coding sequence of the human Bcl‐2 gene
Authors: Lang Georgina , Gombert Wendy M. , Gould Hannah J. 
Published: December 2004

SummaryWe investigated the protein‐binding sites in a DNAse I hypersensitive site associated with bcl‐2 gene expression in human B cells. We mapped this hypersensitive site to the coding sequence of exon 2 of the bcl‐2 gene in the bcl‐2‐expressing REH B‐cell line. Electrophoretic mobility shift assays (EMSAs) with extracts from REH cells revealed three previously unrecognized B‐Myb‐binding sites in this sequence. The protein was identified as B‐Myb by using a specific antibody and EMSAs. Accordingly, the levels of B‐Myb and bcl‐2 proteins, and of Myb EMSA activity, were correlated over a wide range of cell lines, representing different stages of B‐cell development. Transfection of REH cells with antisense B‐myb down‐regulated EMSA activity and the level of bcl‐2, and led to the apoptosis of REH cells. Transfection of the bcl‐2‐non‐expressing RPMI 8226 cell line with a B‐Myb expression vector induced B‐Myb EMSA activity and the expression of bcl‐2. Reporter assays indicated that the HSS8 sequence containing the three B‐Myb sites may act as an enhancer when it is linked to the bcl‐2 gene promoter. Interaction of B‐Myb with HSS8 may enhance bcl‐2 gene expression by co‐operating with positive regulatory elements (e.g. previously identified B‐Myb response elements) or silencing negative response elements in the bcl‐2 gene promoter.
Differential targeting of GSH1 and GSH2 is achieved by multiple transcription initiation: implications for the compartmentation of glutathione biosynthesis in the Brassicaceae
Authors: Wachter Andreas , Wolf Sebastian , Steininger Heike , Bogs Jochen , Rausch Thomas 
Published: December 2004

SummaryThe genome of Arabidopsis thaliana reveals that in this species the enzymes of glutathione biosynthesis, GSH1 and GSH2, are encoded by single genes. In silico analysis predicts proteins with putative plastidic transit peptides (TP) for both genes, but this has not been experimentally verified. Here we report a detailed analysis of the 5′ends of GSH1 and GSH2 mRNAs and demonstrate the subcellular targeting of the proteins encoded by different transcript types. GSH1 transcript analysis revealed two mRNA populations with short and long 5′‐UTRs, respectively, both including the entire TP sequence. The ratio of long/total GSH1 transcripts was subject to developmental regulation. Transient transformation experiments with reporter gene fusions, bearing long or short 5′‐UTRs, indicated an exclusive targeting of GSH1 to the plastids. Corroborating these results, endogenous and ectopically expressed GSH1 proteins were always present as a single polypeptide species with the size expected for correctly processed GSH1. Finally, the plastidic GSH1 localization was confirmed by immunocytochemistry. Similar to GSH1, multiple transcript populations were found for GSH2. However, here the prevalent shorter transcripts lacked a complete TP sequence. As expected, the large (but less abundant) transcript encoded a plastidic GSH2 protein, whereas GSH2 synthesized from the shorter transcript was targeted to the cytosol. The implications of the results for the compartmentation and regulation of GSH synthesis are discussed.
Essential role of the V‐ATPase in male gametophyte development
Authors: Dettmer Jan , Schubert Daniel , Calvo‐Weimar Olga , Stierhof York‐Dieter , Schmidt Renate , Schumacher Karin 
Published: December 2004

SummaryIntracellular pH homeostasis is a prerequisite for biological processes and requires the action of proton pumps. The vacuolar H+‐ATPase (V‐ATPase) is involved in regulating pH in endomembrane compartments of all eukaryotic cells. In plants, there is an additional endomembrane proton pump, H+‐pyrophosphatase (H+‐PPase). However, the relative roles of the two types of pumps in endomembrane acidification and energization of secondary active transport are unclear. Here, we show that a strong T‐DNA insertion allele of VHA‐A, the single copy gene encoding the catalytic subunit of the Arabidopsis V‐ATPase, causes complete male and partial female gametophytic lethality. Severe changes in the morphology of Golgi stacks and Golgi‐derived vesicles in male gametophytes are the first visible symptoms of cell degeneration leading to a failure to develop mature pollen. Similar effects on Golgi morphology were observed in pollen tubes when growth was blocked by Concanamycin A, a specific V‐ATPase inhibitor. Taken together, our results suggests that V‐ATPase function is essential for Golgi organization and development of the male gametophyte.
Asthma phenotypes in Niue Islanders
Authors: ABBOTT William G. H. , WINSHIP Ingrid M. , WILSHER Margaret L. , NILAU Malama , TUKUITONGA Colin F. 
Published: December 2004

Objective:  The aim of this study was to identify asthma phenotypes in patients of Niue Island ancestry that might be suitable for susceptibility gene mapping studies.Methodology:  Two hundred and sixteen Niue Islanders with physician‐diagnosed asthma that was not secondary to other medical conditions were recruited through community organisations. Fifty‐one of the subjects with asthma were resident on Niue Island and 165 in New Zealand. Each subject was interviewed and tested for atopy, serum [IgE] (5% quantile, median, 95% quantile) and lung function.Results:  There were two groups of subjects defined by an age of onset of asthma less than 12 years of age (childhood‐onset, boys:girls 64:65) and greater than 12 years of age (adult‐onset, men:women 11:76). A positive response (wheal > 3 mm) to at least one aeroallergen was seen in 181 patients, with 168/181 (92.8%) responding to house dust mite. Twenty‐eight subjects with asthma were non‐atopic (no detectable wheal) and the atopy status of seven subjects with asthma could not be determined (wheal < 3 mm). In childhood‐onset asthma, serum IgE levels were higher (P < 0.0001) in subjects with atopic than in subjects with non‐atopic asthma. In adult‐onset asthma, serum IgE levels were higher (P < 0.0001) in subjects with atopic asthma than in either subjects with non‐atopic asthma or matched non‐atopic subjects without asthma. The asthma phenotypes in Niue Island and New Zealand residents were similar.Conclusions:  Both atopic and non‐atopic asthma phenotypes exist in Niue Islanders resident in Niue and New Zealand. The potential for mapping asthma susceptibility genes in this isolated population is discussed.
Prediction equations for pulmonary function values in healthy young Iranians aged 8–18 years
Authors: BOSKABADY Mohammad Hossein , TASHAKORY Abulghasem , MAZLOOM Reza , GHAMAMI Gity 
Published: December 2004

Objective:  Pulmonary function test (PFT) variables are dependent on height, age and gender. In addition, there is evidence of PFT variation in different ethnic groups. Prediction equations for PFT from a healthy, non‐smoking, urban young population in the city of Mashhad (north‐east Iran) have been derived.Methodology:  Prediction equations for normal pulmonary function were derived from 336 healthy, non‐smoking subjects, including 187 males (height 103–188.5 cm) and 149 females (height 104–183 cm) aged 8–18 years. The subjects underwent measurement of spirometric flow and volume. The following variables were measured: FVC, FEV1, maximal mid‐expiratory flow (MMEF), PEF, maximal expiratory flow at 75, 50 and 25% of the FVC (MEF75, MEF50, and MEF25, respectively), tidal volume (VT), inspiratory reserve volume (IRV), expiratory reserve volume (ERV), inspiratory capacity (IC), and vital capacity (VC). Regression analysis using height and age as independent variables was applied to provide predicted values for both genders.Results:  There were positive correlations for each pulmonary function variable with height and age. The largest positive correlations were found for FEV1 with height and age, in both genders. Comparison of PFT variables derived from the equations obtained in the present study showed significant differences to those calculated from several previously published equations (P < 0.001 for most variables). For example, the values of FVC and FEV1 derived from the equations obtained in the present study were 2.83 ± 0.99 and 2.50 ± 0.89 for males, and 2.41 ± 0.54 and 2.19 ± 0.53 for females, while the values derived from the equations of the European Community for Steel and Coal study were 3.12 ± 1.06 and 2.62 ± 0.89 for males and 2.79 ± 0.67 and 3.35 ± 0.57 for females, respectively.Conclusions:  A set of PFT reference values and prediction equations for both genders has been derived using a relatively large, healthy, non‐smoking Iranian young population, and has generated results that differ from several other prediction equations.