bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rapid self-assembly of DNA on a microfluidic chip
Authors: Zheng Yao , Footz Tim , Manage Dammika P , Backhouse Christopher James 
Published: February 2005

Abstract
Background
DNA self-assembly methods have played a major role in enabling methods for acquiring genetic information without having to resort to sequencing, a relatively slow and costly procedure. However, even self-assembly processes tend to be very slow when they rely upon diffusion on a large scale. Miniaturisation and integration therefore hold the promise of greatly increasing this speed of operation.

Results
We have developed a rapid method for implementing the self-assembly of DNA within a microfluidic system by electrically extracting the DNA from an environment containing an uncharged denaturant. By controlling the parameters of the electrophoretic extraction and subsequent analysis of the DNA we are able to control when the hybridisation occurs as well as the degree of hybridisation. By avoiding off-chip processing or long thermal treatments we are able to perform this hybridisation rapidly and can perform hybridisation, sizing, heteroduplex analysis and single-stranded conformation analysis within a matter of minutes. The rapidity of this analysis allows the sampling of transient effects that may improve the sensitivity of mutation detection.

Conclusions
We believe that this method will aid the integration of self-assembly methods upon microfluidic chips. The speed of this analysis also appears to provide information upon the dynamics of the self-assembly process.
The utility of pathway selective estrogen receptor ligands that inhibit nuclear factor-κB transcriptional activity in models of rheumatoid arthritis
Authors: Keith James C , Albert Leo M , Leathurby Yelena , Follettie Max , Wang Lili , Borges-Marcucci Lisa , Chadwick Christopher C , Steffan Robert J , Harnish Douglas C 
Published: February 2005

AbstractRheumatoid arthritis (RA) is a chronic inflammatory disease that produces synovial proliferation and joint erosions. The pathologic lesions of RA are driven through the production of inflammatory mediators in the synovium mediated, in part, by the transcription factor NF-κB. We have identified a non-steroidal estrogen receptor ligand, WAY-169916, that selectively inhibits NF-κB transcriptional activity but is devoid of conventional estrogenic activity. The activity of WAY-169916 was monitored in two models of arthritis, the HLA-B27 transgenic rat and the Lewis rat adjuvant-induced model, after daily oral administration. In both models, a near complete reversal in hindpaw scores was observed as well as marked improvements in the histological scores. In the Lewis rat adjuvant model, WAY-169916 markedly suppresses the adjuvant induction of three serum acute phase proteins: haptoglobin, α1-acid glycoprotein (α1-AGP), and C-reactive protein (CRP). Gene expression experiments also demonstrate a global suppression of adjuvant-induced gene expression in the spleen, liver, and popliteal lymph nodes. Finally, WAY-169916 was effective in suppressing tumor necrosis factor-α-mediated inflammatory gene expression in fibroblast-like synoviocytes isolated from patients with RA. Together, these data suggest the utility of WAY-169916, and other compounds in its class, in treating RA through global suppression of inflammation via selective blockade of NF-κB transcriptional activity.
Clinical response to discontinuation of anti-TNF therapy in patients with ankylosing spondylitis after 3 years of continuous treatment with infliximab
Authors: Baraliakos Xenofon , Listing Joachim , Brandt Jan , Rudwaleit Martin , Sieper Joachim , Braun Juergen 
Published: February 2005

AbstractWe analyzed the clinical response and the time to relapse after discontinuation of continuous long-term infliximab therapy in patients with ankylosing spondylitis (AS). After 3 years of infliximab therapy, all AS patients (n = 42) discontinued treatment (time point (TP)1) and were visited regularly for 1 year in order to assess the time to relapse (TP2). Relapse was defined as an increase to a value ≥ 4 on the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and a physician's global assessment ≥ 4 according to the recommendations of the Assessments in Ankylosing Spondylitis (ASAS) working group. After 52 weeks, 41 of the 42 patients (97.6%) had to be reinfused because of relapse. The mean change in the BASDAI between TP1 and TP2 was 3.6 ± 1.7 and that in the physician's global assessment was 4.4 ± 1.8 (both P < 0.001). The mean time to relapse was 17.5 weeks (± 7.9 weeks, range 7 to 45). Ten patients (24%) showed a relapse within 12 weeks and 38 patients (90.5%), within 36 weeks. After 52 weeks, only one patient had remained in ongoing remission without further treatment with anti-tumor-necrosis factor. Patients who were in partial remission according to the ASAS criteria and those with normal C-reactive protein levels at the time point of withdrawal had longer times to relapse after discontinuation of the treatment. Retreatment with infliximab was safe and resulted in clinical improvement in all patients to a state similar to that before the treatment was stopped. Discontinuation of long-term therapy with infliximab eventually led to relapse of disease activity in all patients but one.
Small GTP-binding protein Rho-mediated signaling promotes proliferation of rheumatoid synovial fibroblasts
Authors: Nakayamada Shingo , Kurose Hitoshi , Saito Kazuyoshi , Mogami Akira , Tanaka Yoshiya 
Published: February 2005

AbstractRho is a major small GTP-binding protein that is involved in the regulation of various cell functions, including proliferation and cell migration, through activation of multiple signaling molecules in various types of cells. We studied its roles in synovial fibroblasts (SFs) in patients with rheumatoid arthritis (RA) and clarified its relevance to RA synovitis, with the following results. 1)We found that the thrombin receptor was overexpressed on RA synovial fibroblasts (RA SFs) and that thrombin induced a marked proliferation and progression of the cell cycle to the S phase in these cells. 2)We also found that thrombin efficiently activated Rho. 3)Rho activation and proliferation and the progression of the cell cycle to the S phase were completely blocked by p115RGS (an N-terminal regulator of the G-protein signaling domain of p115RhoGEF) and by the C-terminal fragments of Gα13 (an inhibitor of the interaction of receptors with G13). 4)Thrombin induced the secretion of IL-6 by RA SFs, but this action was blocked by p115RGS or Gα13. Our findings show that the actions of thrombin on the proliferation of RA SFs, cell-cycle progression to the S phase, and IL-6 secretion were mainly mediated by the G13 and RhoGEF pathways. These results suggest that p115RGS and Gα13 could be potent inhibitors of such functions. A rational design of future therapeutic strategies for RA synovitis could perhaps include the exploitation of the Rho pathway to directly reduce the growth of synovial cells.
Peripheral blood but not synovial fluid natural killer T cells are biased towards a Th1-like phenotype in rheumatoid arthritis
Authors: Linsen Loes , Thewissen Marielle , Baeten Kurt , Somers Veerle , Geusens Piet , Raus Jef , Stinissen Piet 
Published: February 2005

AbstractNatural killer T (NKT) cells have been implicated in the regulatory immune mechanisms that control autoimmunity. However, their precise role in the pathogenesis of rheumatoid arthritis (RA) remains unclear. The frequency, cytokine profile and heterogeneity of NKT cells were studied in peripheral blood mononuclear cells (PBMCs) from 23 RA patients and 22 healthy control individuals, including paired PBMC–synovial fluid samples from seven and paired PBMC–synovial tissue samples from four RA patients. Flow cytometry revealed a decreased frequency of NKT cells in PBMCs from RA patients. NKT cells were present in paired synovial fluid and synovial tissue samples. Based on the reactivity of PBMC-derived NKT cells toward α-galactosylceramide, RA patients could be divided into responders (53.8%) and nonresponders (46.2%). However, NKT cells isolated from synovial fluid from both responders and nonresponders expanded upon stimulation with α-galactosylceramide. Analysis of the cytokine profile of CD4+ and CD4- PBMC derived NKT cell lines from RA patients revealed a significantly reduced number of IL-4 producing cells. In contrast, synovial fluid derived NKT cell lines exhibited a Th0-like phenotype, which was comparable to that in healthy control individuals. This suggests that synovial fluid NKT cells are functional, even in patients with nonresponding NKT cells in their blood. We conclude that, because the number of Vα24+Vβ11+CD3+ NKT cells is decreased and the cytokine profile of blood-derived NKT cells is biased toward a Th1-like phenotype in RA patients, NKT cells might be functionally related to resistance or progression of RA. Providing a local boost to the regulatory potential of NKT cells might represent a useful candidate therapy for RA.
A web tool for finding gene candidates associated with experimentally induced arthritis in the rat
Authors: Andersson Lars , Petersen Greta , Johnson Per , Ståhl Fredrik 
Published: February 2005

AbstractRat models are frequently used for finding genes contributing to the arthritis phenotype. In most studies, however, limitations in the number of animals result in a low resolution. As a result, the linkage between the autoimmune experimental arthritis phenotype and the genomic region, that is, the quantitative trait locus, can cover several hundred genes. The purpose of this work was to facilitate the search for candidate genes in such regions by introducing a web tool called Candidate Gene Capture (CGC) that takes advantage of free text data on gene function. The CGC tool was developed by combining genomic regions in the rat, associated with the autoimmune experimental arthritis phenotype, with rat/human gene homology data, and with descriptions of phenotypic gene effects and selected keywords. Each keyword was assigned a value, which was used for ranking genes based on their description of phenotypic gene effects. The application was implemented as a web-based tool and made public at http://ratmap.org/cgc. The CGC application ranks gene candidates for 37 rat genomic regions associated with autoimmune experimental arthritis phenotypes. To evaluate the CGC tool, the gene ranking in four regions was compared with an independent manual evaluation. In these sample tests, there was a full agreement between the manual ranking and the CGC ranking for the four highest-ranked genes in each test, except for one single gene. This indicates that the CGC tool creates a ranking very similar to that made by human inspection. The exceptional gene, which was ranked as a gene candidate by the CGC tool but not in the manual evaluation, was found to be closely associated with rheumatoid arthritis in additional literature studies. Genes ranked by the CGC tools as less likely gene candidates, as well as genes ranked low, were generally rated in a similar manner to those done manually. Thus, to find genes contributing to experimentally induced arthritis, we consider the CGC application to be a helpful tool in facilitating the evaluation of large amounts of textual information.
Body fatness during childhood and adolescence and incidence of breast cancer in premenopausal women: a prospective cohort study
Authors: Baer Heather J , Colditz Graham A , Rosner Bernard , Michels Karin B , Rich-Edwards Janet W , Hunter David J , Willett Walter C 
Published: February 2005

Abstract
Introduction
Body mass index (BMI) during adulthood is inversely related to the incidence of premenopausal breast cancer, but the role of body fatness earlier in life is less clear. We examined prospectively the relation between body fatness during childhood and adolescence and the incidence of breast cancer in premenopausal women.

Methods
Participants were 109,267 premenopausal women in the Nurses' Health Study II who recalled their body fatness at ages 5, 10 and 20 years using a validated 9-level figure drawing. Over 12 years of follow up, 1318 incident cases of breast cancer were identified. Cox proportional hazards regression was used to compute relative risks (RRs) and 95% confidence intervals (CIs) for body fatness at each age and for average childhood (ages 5–10 years) and adolescent (ages 10–20 years) fatness.

Results
Body fatness at each age was inversely associated with premenopausal breast cancer incidence; the multivariate RRs were 0.48 (95% CI 0.35–0.55) and 0.57 (95% CI 0.39–0.83) for the most overweight compared with the most lean in childhood and adolescence, respectively (P for trend < 0.0001). The association for childhood body fatness was only slightly attenuated after adjustment for later BMI, with a multivariate RR of 0.52 (95% CI 0.38–0.71) for the most overweight compared with the most lean (P for trend = 0.001). Adjustment for menstrual cycle characteristics had little impact on the association.

Conclusion
Greater body fatness during childhood and adolescence is associated with reduced incidence of premenopausal breast cancer, independent of adult BMI and menstrual cycle characteristics.
Protein kinase Cδ regulates p67phox phosphorylation in human monocytes
Authors: Zhao Xiaoxian , Xu Bo , Bhattacharjee Ashish , Oldfield Claudine M , Wientjes Frans B , Feldman Gerald M , Cathcart Martha K 
Published: February 2005

AbstractPhosphorylation of the reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase components p67phox and p47phox accompanies the assembly and activation of this enzyme complex. We have previously reported that activation of human monocytes with opsonized zymosan (ZOP), a potent stimulator of NADPH oxidase activity, results in the phosphorylation of p67phox and p47phox. In this study, we investigated the regulation of p67phox phosphorylation. Although protein kinase C (PKC)α has previously been shown to regulate NADPH oxidase activity, we found that inhibition of PKCα had no effect on p67phox phosphorylation. Our studies demonstrate that pretreatment of monocytes with antisense oligodeoxyribonucleotides specific for PKCδ or rottlerin, a selective inhibitor for PKCδ, inhibited the phosphorylation of p67phox in monocytes, and Go6976, a specific inhibitor for conventional PKCs, PKCα and PKCβ, had no such inhibitory effect. Additional studies indicate that ZOP stimulation of monocytes induces PKCδ and p67phox to form a complex. We also demonstrate that lysates from activated monocytes as well as PKCδ immunoprecipitates from activated monocytes can phosphorylate p67phox in vitro and that pretreatment of monocytes with rottlerin blocked the phosphorylation in each case. We further show that recombinant PKCδ can phosphorylate p67phox in vitro. Finally, we show that PKCδ-deficient monocytes produce significantly less superoxide anion in response to ZOP stimulation, thus emphasizing the functional significance of the PKCδ regulation of p67phox phosphorylation. Taken together, this is the first report to describe the requirement of PKCδ in regulating the phosphorylation of p67phox and the related NADPH oxidase activity in primary human monocytes.
Fetal and neonatal murine skin harbors Langerhans cell precursors
Authors: Chang-Rodriguez S , Hoetzenecker W , Schwärzler C , Biedermann T , Saeland S , Elbe-Bürger A 
Published: February 2005

AbstractResident epidermal Langerhans cells (LC) in adult mice express ADPase, major histocompatibility complex (MHC) class II, and CD205 and CD207 molecules, while the first dendritic leukocytes that colonize the fetal and newborn epidermis are only ADPase+. In this study, we tested whether dendritic epidermal leukocytes (DEL) are end-stage cells or represent LC precursors. In epidermal sheets of fetal and neonatal mice, we found no apoptotic leukocytes, suggesting that these cells do not die in situ. To address whether DEL can give rise to LC, sorted DEL from murine newborn skin were cultured with cytokines used to generate LC from human CD34+ precursors. After 7–14 days, DEL proliferated and acquired the morphology and phenotype of cells reminiscent of LC. In concordance with this finding, we show that neonatal epidermis harbors 10–20 times the number of cycling MHC class II+ leukocytes as adult tissue. To test whether LC can differentiate from skin precursors in vivo, we developed a transplantation model. As it was impossible to transplant fetal epidermis, whole fetal skin was grafted onto adult severe combined immunodeficient mice. As opposed to the uniform absence of donor LC at the time of transplantation, examination of the epidermis from the grafts after 2–4 weeks revealed MHC class II+ donor cells, which had acquired CD205 and CD207, thus qualifying them as LC. Finally, we present evidence that endogenous LC persist in skin grafts for the observation period of 45 days. These studies show that hematopoietic precursors seed the skin during embryonic life and can give rise to LC.
Evaluation of traumatic brain injured patients in correlation with functional status by localized 1H-MR spectroscopy
Authors: Yoon Se Jin , Lee Jung Hee , Kim Sang Tae , Chun Min Ho 
Published: February 2005

Objective: To determine whether proton magnetic resonance spectroscopy (1H-MRS) could be a useful tool for detecting microscopic diffuse axonal injury to evaluate the functional status of patients with traumatic brain injury (TBI). Design: A comparative study. Setting: An inpatient rehabilitation unit in Korea. Subjects: We examined eight adult patients who had severe TBI approximately five months before. Fourteen normal controls were employed for comparison. Main measures: Image-guided localized in vivo 1H-MRS was performed in the parietal white matter and occipital grey matter regions in brain in which no definite abnormalities in MR imaging were found at the time of 1H-MRS examination. We evaluated functional status for all patients with the Functional Independence Measure (FIM) on the same day as the 1H-MRS examination and compared the results. Results: In the parietal white matter, the [N-acetyl aspartate/creatine] ratios were significantly lower, and the [choline/creatine] and [myo-inositol/creatine] ratios were significantly higher than those of normal controls. Significant correlations of the [N-acetyl aspartate/creatine] and [myo-inositol/creatine] ratios in the parietal white matter with FIM scores were observed (p≤0.05). Conclusions: A spectral feature of the decreased [N-acetyl aspartate/creatine] and increased [choline/creatine] and [myo-inositol/creatine] ratios in parietal white matter may be a marker for diffuse axonal injury in patients with TBI and has a significant correlation with the functional status of the patients. Localized 1H-MRS has the potential to be used for detecting diffuse axonal injury in vivo in TBI patients, which can be used to guide evaluation of the functional status of TBI patients receiving rehabilitation.
The reliability of balance, mobility and self-care measures in a population of adults with a learning disability known to a physiotherapy service
Authors: Sackley Cath , Richardson Patricia , McDonnell Karen , Ratib Sonia , Dewey Michael , Hill Helen J 
Published: February 2005

Objective: To estimate the reliability of three measures of balance, mobility and activity for use in clinical and research physiotherapy, with adults with a learning disability. Design: Prospective study to investigate test-retest and inter-rater reliability. Setting: Participants' homes and day centres. Measures: The Berg Balance Scale (BBS), the Rivermead Mobility Index (RMI) and the Barthel Activities of Daily Living Index (BI). Participants: Of the 181 adults known to the Nottingham Community Physiotherapy Service for Adults with Learning Disabilities, 64 with a known Rivermead Mobility score of less than three were excluded. Of 117 randomized, a further 21 were found to fail this criteria, 27 had acute medical, social or behavioural problems, 22 were unable to participate or refused: therefore 47 entered the study. Methods: Participants were visited in their own homes by two researchers on two occasions, one week apart and rated independently by each rater. Agreement was assessed with the kappa statistic (k) and percentage agreement for each item in each scale, and described using standard classification. Intraclass correlation coefficients for inter-rater and test-retest total scores and average differences of total scores, their standard deviations and limits of agreement, were calculated. Results: For inter-rater observations, the Barthel Index and the Rivermead Mobility Index had almost perfect agreement (k=0.86–1.00 and 0.89–1.00 respectively), with the Berg Balance Scale having substantial to almost perfect agreement (k=0.74–1.00). For test–retest comparisons, both the Barthel Index and the Rivermead Mobility Index demonstrated moderate to almost perfect agreement (k=0.57–1.00 and 0.45–1.00 respectively). Kappa scores for the Berg Balance Scale varied from low to almost perfect agreement (k=0.37–1.00). Conclusions: The Berg Balance Scale, Rivermead Mobility Index and Barthel Activities of Daily Living Index are all reliable clinical and research tools for physiotherapists working with adults with learning disabilities.
Measuring energy expenditure using heart rate to assess the effects of wheelchair tyre pressure
Authors: Sawatzky B J , Miller W C , Denison I 
Published: February 2005

Objective: To investigate the effects of wheelchair tyre pressure on mechanics and energy and explore the use of heart rate as a measurement of energy expenditure. Design: A single factor repeated measures design was used. Four tyre pressures (100, 75, 50, 25 psi) represented a change of workload. Each subject wheeled at a constant self-selected wheeling velocity for 8 min. A total of four trials were completed with a 10-min rest between trials. Oxygen consumption, heart rate and distance travelled were collected during each trial. Subjects: Three women and 11 men with spinal cord injury. The mean age for the whole group was 34.5 years. The range of lesion level was T4-L1. Results: There was a significant increase is energy expenditure when tyres were deflated to 50 psi from 100 psi. The mean correlation between heart rate and oxygen consumption was 0.74 for all subjects. For the subjects with lesions above T6 and T6 and below the correlations were 0.55 and 0.82, respectively. Conclusions: Tyre pressures below 50% inflation add an additional 25% increase in energy expenditure during wheeling. This could be detected using oxygen consumption or heart rate, as heart rate was shown to have a good correlation with oxygen consumption in the spinal cord injured with lesions below T5. Heart rate does have its limitations and it should only be used to measure within-subject differences.