bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low‐dose prednisolone in addition to the initial disease‐modifying antirheumatic drug in patients with early active rheumatoid arthritis reduces joint destruction and increases the remission rate: A two‐year randomized trial
Authors: Svensson Björn , Boonen Annelies , Albertsson Kristina , van der Heijde Désirée , Keller Catharina , Hafström Ingiäld ,   for the BARFOT Study Group
Published: October 2005

AbstractObjectiveTo assess the efficacy of low‐dose prednisolone on joint damage and disease activity in patients with early rheumatoid arthritis (RA).MethodsAt the start of their initial treatment with a disease‐modifying antirheumatic drug (DMARD), patients with early (duration ≤1 year) active RA were randomly assigned to receive either 7.5 mg/day prednisolone or no prednisolone for 2 years. Radiographs of the hands and feet were obtained at baseline and after 1 and 2 years and scored according to the Sharp score as modified by van der Heijde. Remission was defined as a Disease Activity Score in 28 joints of <2.6. Bone mineral density was measured by dual x‐ray absorptiometry at baseline and after 2 years.ResultsOf the 250 patients included, 242 completed the study and 225 had radiographs available both at baseline and at 2 years. At 2 years, the median and interquartile range (IQR) change in total Sharp score was lower in the prednisolone group than in the no‐prednisolone group (1.8 [IQR 0.5–6.0] versus 3.5 [IQR 0.5–10];P= 0.019). In the prednisolone group, there were fewer newly eroded joints per patient after 2 years (median 0.5 [IQR 0–2] versus 1.25 [IQR 0–3.25];P= 0.007). In the prednisolone group, 25.9% of patients had radiographic progression beyond the smallest detectable difference compared with 39.3% of patients in the no‐prednisolone group (P= 0.033). At 2 years, 55.5% of patients in the prednisolone group had achieved disease remission, compared with 32.8% of patients in the no‐prednisolone group (P= 0.0005). There were few adverse events that led to withdrawal. Bone loss during the 2‐year study was similar in the 2 treatment groups.ConclusionPrednisolone at 7.5 mg/day added to the initial DMARD retarded the progression of radiographic damage after 2 years in patients with early RA, provided a high remission rate, and was well tolerated. Therefore, the data support the use of low‐dose prednisolone as an adjunct to DMARDs in early active RA.
Relative contribution of cardiovascular risk factors and rheumatoid arthritis clinical manifestations to atherosclerosis
Authors: del Rincón Inmaculada , Freeman Gregory L. , Haas Roy W. , O'Leary Daniel H. , Escalante Agustín 
Published: October 2005

AbstractObjectiveTo estimate the contribution of cardiovascular (CV) risk factors and rheumatoid arthritis (RA) disease manifestations to atherosclerosis in RA.MethodsWe used high‐resolution carotid ultrasound to measure the carotid intima‐media thickness (IMT) and plaque in 631 RA patients. Using R2 measures from multivariable models, we estimated the contribution of demographic characteristics (age, sex, and ethnic group), CV risk factors (diabetes mellitus, hypercholesterolemia, cigarette smoking, hypertension, and body mass index, and RA manifestations (joint tenderness, swelling, and deformity, nodules, erythrocyte sedimentation rate [ESR], C‐reactive protein, rheumatoid factor, the HLA–DRB1 shared epitope, and cumulative glucocorticoid dose) to each of the outcomes. Estimates were obtained in the full sample, and within strata defined by age, sex, and ethnic group. We tested for interaction between CV risk factors and RA manifestations.ResultsThe contribution of demographic factors, CV risk factors, and RA manifestations to IMT and plaque R2 varied depending on the patients' age stratum. Demographic features explained 11–16% of IMT variance, CV risk factors explained 4%–12%, and RA manifestations explained 1–6%. The greatest contribution of RA manifestations occurred in the youngest age group, while that of CV risk factors occurred in the older age groups. Results for carotid plaque were similar. There was a significant interaction between the number of CV risk factors present and the ESR, suggesting that the ESR's effect on IMT varied according to the number of CV risk factors.ConclusionBoth established CV risk factors and manifestations of RA inflammation contribute significantly to carotid atherosclerosis in RA, and may modify one another's effects. These findings may have implications regarding the prevention of atherosclerosis in RA.
Somatic mosaicism of CIAS1 in a patient with chronic infantile neurologic, cutaneous, articular syndrome
Authors: Saito Megumu , Fujisawa Akihiro , Nishikomori Ryuta , Kambe Naotomo , Nakata‐Hizume Mami , Yoshimoto Momoko , Ohmori Katsuyuki , Okafuji Ikuo , Yoshioka Takakazu , Kusunoki Takashi , Miyachi Yoshiki , Heike Toshio , Nakahata Tatsutoshi 
Published: October 2005

AbstractChronic infantile neurologic, cutaneous, articular syndrome (CINCA syndrome) is a severe inflammatory disease that was recently found to be associated with mutations in CIAS1. However, CIAS1 mutations have been detected in only half of CINCA syndrome patients, and it remains unclear which genes are responsible for the syndrome in the remaining patients. We describe here a patient with CINCA syndrome who exhibited CIAS1 somatic mosaicism. We genetically analyzed the CIAS1 gene in various blood cells and the buccal mucosa of the patient. The production of interleukin‐1β (IL‐1β) by peripheral blood mononuclear cells (PBMCs) was measured by enzyme‐linked immunosorbent assay, and the ability of the mutant CIAS1 gene to enhance ASC‐dependent NF‐κB activation was assessed to confirm that the mutations of CIAS1 found were responsible for the patient's clinical manifestations of the CINCA syndrome. The patient had 1 heterologous single‐nucleotide polymorphism, 587G>A (S196N), and 1 heterologous mutation, 1709A>G (Y570C), in exon 3 of CIAS1. The latter mutation was found to occur as somatic mosaicism. The patient's PBMCs produced a large amount of IL‐1β in the absence of stimulation, unlike those from controls or from his mother, who also bore the S196N polymorphism. In addition, the Y570C mutation (with or without the S196N polymorphism) increased the ability of CIAS1 to induce ASC‐dependent NF‐κB activation, unlike the wild‐type gene or the gene bearing the S196N polymorphism alone. The findings in this patient indicate that somatic mosaicism is one reason CIAS1 mutations have not been detected in some patients with CINCA syndrome.
Hip abduction moment and protection against medial tibiofemoral osteoarthritis progression
Authors: Chang Alison , Hayes Karen , Dunlop Dorothy , Song Jing , Hurwitz Debra , Cahue September , Sharma Leena 
Published: October 2005

AbstractObjectiveTo test the hypothesis that a greater peak internal hip abduction moment is associated with a reduced likelihood of ipsilateral medial tibiofemoral osteoarthritis (OA) progression.MethodsFifty‐seven persons with knee OA (by definite osteophyte presence and symptoms) were evaluated. Baseline assessments included kinematic and kinetic gait parameters, obtained with an optoelectronic camera system and force platform, with inverse dynamics used to calculate 3‐dimensional moments at the joints; pain, using a separate visual analog scale for each knee; and alignment, using full‐limb radiographs. Radiographs of the knee in a semiflexed position, with fluoroscopic confirmation of tibial rim alignment, were obtained at baseline and 18 months later. Disease progression was defined as worsening of the grade of medial joint space narrowing. Logistic regression obtained with generalized estimating equations was used to estimate odds ratios (ORs) for progression per unit of hip abduction moment, after excluding knees with the worst joint space grade at baseline (which could not progress).ResultsThe 57 participants (63% women) with mild to moderate OA had a mean age of 67 years and a mean body mass index of 29. A greater internal hip abduction moment during gait was associated with a reduced likelihood of medial tibiofemoral OA progression, with OR/unit hip abduction moment of 0.52 and a 95% confidence interval (95% CI) of 0.32–0.85. This protective effect persisted after adjustment for age, sex, walking speed, knee pain severity, physical activity, varus malalignment severity, hip OA presence, and hip OA symptom presence, with an adjusted OR of 0.43 a 95% CI of 0.22–0.81.ConclusionA greater hip abduction moment during gait at baseline protected against ipsilateral medial OA progression from baseline to 18 months. The likelihood of medial tibiofemoral OA progression was reduced 50% per 1 unit of hip abduction moment.
Linkage at 5q14.3–15 in multiplex systemic lupus erythematosus pedigrees stratified by autoimmune thyroid disease
Authors: Namjou Bahram , Kelly Jennifer A. , Kilpatrick Jeff , Kaufman Kenneth M. , Nath Swapan K. , Scofield R. Hal , Harley John B. 
Published: October 2005

AbstractObjectiveTo identify genetic effects potentially shared between systemic lupus erythematosus (SLE) and autoimmune thyroiditis (AITD).MethodsFamilies from the Lupus Multiplex Registry and Repository were studied in which there was at least 1 member who had both SLE and AITD (Graves' disease or Hashimoto thyroiditis). Genome scan genotyping findings in these pedigrees were evaluated for evidence of genetic linkage, by the maximum‐likelihood parametric method. Nineteen pedigrees were used in the initial genome scan. Subsequently, an independent sample of 16 pedigrees was used to replicate findings.ResultsStudies of the first set of 19 pedigrees yielded a 2‐point parametric logarithm of odds (LOD) of 4.97, which was independently confirmed in the replication sample of 16 pedigrees (LOD 2.89). For all 35 pedigrees together, the 2‐point LOD was 7.86, under a dominant model used for screening with 90% penetrance and a disease allele frequency of 10%. The multipoint locus homogeneity LOD in the 35 pedigrees was 6.90 (α = 1.0) at 5q14.3–15 between D5S1725 and D5S1453, a 12‐cM interval, with the peak at D5S1462 at 96.64 cM (nonparametric linkage P = 0.00002). Fine mapping further confirmed the genetic linkage effect and narrowed the region likely to contain the gene to ∼5 Mb.ConclusionThese results suggest that stratifying SLE pedigrees by the presence of other autoimmune disorders may facilitate the discovery of genes related to SLE and that 5q14.3–15 harbors a susceptibility gene shared by SLE and AITD.
Very low‐dose prednisolone in early rheumatoid arthritis retards radiographic progression over two years: A multicenter, double‐blind, placebo‐controlled trial
Authors: Wassenberg Siegfried , Rau Rolf , Steinfeld Paul , Zeidler Henning ,   Low‐Dose Prednisolone Therapy Study Group
Published: October 2005

AbstractObjectiveTo assess the effect of 5 mg/day prednisolone on disease progression in patients with early rheumatoid arthritis (RA) receiving standardized disease‐modifying antirheumatic drug (DMARD) therapy.MethodsPatients with active RA of <2 years' duration were randomly assigned in a double‐blinded manner to receive prednisolone or placebo while starting concomitant DMARD therapy (gold sodium thiomalate or methotrexate). Hand and foot radiographs were taken at baseline and at 6, 12, and 24 months and were evaluated according to the Ratingen score and the total modified Sharp/van der Heijde score (SHS).ResultsOf 192 included patients, 166 were available for the intent‐to‐treat analysis (ITT). Seventy‐six patients completed the study per protocol (PP). Radiographic progression (increase in the Ratingen score) was significantly less with prednisolone than with placebo. The difference in the progression rate between the groups was greatest in the first 6 months. At 24 months in the ITT population, the least squares (LS) mean difference was 3.14 (95% confidence interval [95% CI] 0.94, 5.34),P= 0.006. The results were confirmed by the total SHS in the ITT population (LS mean difference 7.20 [95% CI 0.93, 13.47],P= 0.022) and with the PP population. Clinical and functional outcomes tended to be better and the rate of remissions was higher in the prednisolone group. Side effects were observed more frequently in the prednisolone group than in the control group: weight gain (4 versus 0 patients), hypertension (6 versus 2 patients), glaucoma (3 versus 0 patients), Cushing's syndrome (5 versus 0 patients), gastric distress (9 versus 4 patients), and gastric ulcers (only with concomitant nonsteroidal antiinflammatory drug therapy; 3 versus 0 patients). No new lumbar fractures were found in either group.ConclusionThe very low daily dose of 5 mg prednisolone given over 2 years in combination with background DMARD therapy substantially decreased radiographic progression in early RA at low risk.
Systematic review and meta-analysis of the effectiveness of antibiotic prophylaxis in prevention of wound infection after mesh repair of abdominal wall hernia
Authors: Aufenacker T J , Koelemay M J W , Gouma D J , Simons M P 
Published: October 2005

Abstract

Background
The aim was to determine whether systemic antibiotic prophylaxis prevented wound infection after repair of abdominal wall hernia with mesh.

Methods
This was a systematic review of the available literature identified from multiple databases using the terms ‘hernia’ and ‘antibiotic prophylaxis’. Randomized placebo-controlled trials of antibiotic prophylaxis in abdominal wall mesh hernia repair with explicitly defined wound infection criteria and a minimum follow-up of 1 month were included. After independent quality assessment and data extraction, data were pooled for meta-analysis using a random-effects model.

Results
The search process identified eight relevant trials. Two papers on umbilical, incisional or laparoscopic hernias, and six concerning inguinal and femoral (groin) hernias were suitable for meta-analysis. The incidence of infection after groin hernia repair was 38 (3·0 per cent) of 1277 in the placebo group and 18 (1·5 per cent) of 1230 in the antibiotic group. Antibiotic prophylaxis did not significantly reduce the incidence of infection: odds ratio 0·54 (95 per cent confidence interval 0·24 to 1·21); number needed to treat was 74. The number of deep infections was six (0·6 per cent) in the placebo group and three (0·3 per cent) in the antibiotic prophylaxis group: odds ratio 0·50 (95 per cent c.i. 0·12 to 2·09).

Conclusion
Antibiotic prophylaxis did not prevent the occurrence of wound infection after groin hernia surgery. More trials are needed for complete evidence in other areas of abdominal wall hernia.
Challenging the Standard Story of indigenous rights in Aotearoa/New Zealand
Authors: Kirkwood Steve , Liu James H. , Weatherall Ann 
Published: October 2005

AbstractThree public submissions are discursively analysed to understand how history, identity and equality are used to legitimise positions on indigenous rights claims over the foreshore and seabed in Aotearoa/New Zealand. The first submission illustrates the Standard Story of ethnic relations, whereby the ethnic majority is unmarked, colonisation is construed as unrelated to the present, and a tolerant, unified nation is constructed to exclude ‘divisive’ indigenous rights. In contrast, the second submission legitimises the claims by flagging the position of the ethnic majority, construing colonisation as an ongoing process that continues to favour Pakeha (white) New Zealanders over Maori. The third submission works up the similarity between indigenous rights and general property rights, negotiating the relationship between equal treatment and self‐determination to legitimise the claims. We argue that discursive research on discrimination should approach texts as contributions to a dialectics of racism and anti‐racism. This is useful for gaining a better understanding of oppressive discourses, and developing arguments that actively challenge discrimination. The Treaty of Waitangi provides Pakeha New Zealanders with discursive resources for constructing the subject position of a ‘partnership’ with Maori that legitimises the positions of both groups within a shared national identity. Copyright © 2005 John Wiley & Sons, Ltd.
Examining discourses of whiteness and the potential for Reconciliation
Authors: Green Meredith J. , Sonn Christopher C. 
Published: October 2005

AbstractThe aim of this article is to explore how examining discourses of whiteness can contribute to an anti‐racism that does not only focus on those affected by racism, thereby locating the issue with the ‘other’, but also attends to the privilege and dominance that is central to unequal and unfair distributions of power. Based on the discourse analysis (see Henriques, Hollway, Urwin, Venn, & Walkerdine, 1998; Parker, 1992) of interviews and focus groups with white Australians about their involvement in Reconciliation we discuss how by examining discursive negotiations at the micro level we are able to critique dominance and privilege at the macro level. In particular, we identify spaces for the examination and critique of whiteness within white Australians' discursive negotiations of Reconciliation. We also discuss how engagement with Indigenous knowledges is a necessary part of the critique of whiteness. Copyright © 2005 John Wiley & Sons, Ltd.
Break on through to the Other Side—Biophysics and Cell Biology Shed Light on Cell‐Penetrating Peptides
Authors: Fischer Rainer , Fotin‐Mleczek Mariola , Hufnagel Hansjörg , Brock Roland 
Published: October 2005

AbstractCell‐penetrating peptides (CPPs) have become widely used vectors for the cellular import of molecules in basic and applied biomedical research. Despite the broad acceptance of these molecules as molecular carriers, the details of the mode of cellular internalization and membrane permeation remain elusive. Within the last two years endocytosis has been demonstrated to be a route of uptake shared by several CPPs. These findings had a significant impact on CPP research. State‐of‐the‐art cell biology is now required to advance the understanding of the intracellular fate of the CPP and cargo molecules. Owing to their presumed ability to cross lipid bilayers, CPPs also represent highly interesting objects of biophysical research. Numerous studies have investigated structure–activity relationships of CPPs with respect to their ability to bind to a lipid bilayer or to cross this barrier. Endocytosis route only relocates the membrane permeation from the cell surface to endocytic compartments. Therefore, biophysical experiments are key to a mechanistic molecular understanding of the cellular uptake of CPPs. However, biophysical investigations have to consider the molecular environment encountered by a peptide inside and outside a cell. In this contribution we will review biophysical and cell‐biology data obtained for several prominent CPPs. Furthermore, we will summarize recent findings on the cell‐penetrating characteristics of antimicrobial peptides and the antimicrobial properties of CPPs. Peptides of both groups have overlapping characteristics. Therefore, both fields may greatly benefit from each other. The review will conclude with a perspective of how biophysics and cell biology may synergize even more efficiently in the future.
Protein Flexibility and Ligand Rigidity: A Thermodynamic and Kinetic Study of ITAM‐Based Ligand Binding to Syk Tandem SH2
Authors: de Mol Nico J. , Catalina M. Isabel , Dekker Frank J. , Fischer Marcel J. E. , Heck Albert J. R. , Liskamp Rob M. J. 
Published: October 2005

AbstractThe Syk tandem Src homology 2 domain (Syk tSH2) constitutes a flexible protein module involved in the regulation of Syk kinase activity. The Syk tSH2 domain is assumed to function by adapting the distance between its two SH2 domains upon bivalent binding to diphosphotyrosine ligands. A thermodynamic and kinetic analysis of ligand binding was performed by using surface plasmon resonance (SPR). Furthermore, the effect of binding on the Syk tSH2 structural dynamics was probed by hydrogen/deuterium exchange and electrospray mass spectrometry (ESI‐MS). Two ligands were studied:1, a flexible peptide derived from the tSH2 recognition ITAM sequence at the γ chain of the FcεRI‐receptor, and2, a ligand in which the amino acids between the two SH2 binding motifs in ligand1have been replaced by a rigid linker of comparable length. Both ligands display comparable affinity for Syk tSH2 at 25 °C, yet a major difference in thermodynamics is observed. Upon binding of the rigid ligand,2, the expected entropy advantage is not realized. On the contrary,2binds with a considerably higher entropy price of ∼9 kcal mol−1, which is attributed to a further decrease in protein flexibility upon binding to this rigid ligand. The significant reduction in deuterium incorporation in the Syk tSH2 protein upon binding of either1or2, as monitored by ESI‐MS, indicates a major reduction in protein dynamics upon binding. The results are consistent with a two‐step binding model: after an initial binding step, a rapid structural change of the protein occurs, followed by a second binding step. Such a bivalent binding model allows high affinity and fast dissociation kinetics, which are very important in transient signal‐transduction processes.
Design of a Hairpin Polyamide, ZT65B, for Targeting the Inverted CCAAT Box (ICB) Site in the Multidrug Resistant (MDR1) Gene
Authors: Buchmueller Karen L. , Taherbhai Zarmeen , Howard Cameron M. , Bailey Suzanna L. , Nguyen Binh , O’Hare Caroline , Hochhauser Daniel , Hartley John A. , Wilson W. David , Lee Moses 
Published: October 2005

AbstractA novel hairpin polyamide, ZT65B, containing a 3‐methylpicolinate moiety was designed to target the inverted CCAAT box (ICB) of the human multidrug resistance 1 gene (MDR1) promoter. Binding of nuclear factor‐Y (NF‐Y) to the ICB site upregulates MDR1 gene expression and is, therefore, a good target for anticancer therapeutic agents. However, it is important to distinguish amongst different promoter ICB sites so that only specific genes will be affected. All ICB sites have the same sequence but they differ in the sequence of the flanking base pairs, which can be exploited in the design of sequence‐specific polyamides. To test this hypothesis, ten ICB‐containing DNA hairpins were designed with different flanking base pairs; the sequences ICBa and ICBb were similar to the 3′‐ICB site of MDR1 (TGGCT). Thermal‐denaturation studies showed that ZT65B effectively targeted ICBa and ICBb (ΔTM=6.5 and 7.0 °C) in preference to the other DNA hairpins (<3.5 °C), with the exception of ICBc (5.0 °C). DNase I‐footprinting assays were carried out with the topoisomerase IIα‐promoter sequence, which contains five ICB sites; of these, ICB1 and ICB5 are similar to the ICB site of MDR1. ZT65B was found to selectively bind ICB1 and ICB5; footprints were not observed with ICB2, ICB3, or ICB4. A strong, positive induced ligand band at 325 nm in CD studies confirmed that ZT65B binds in the DNA minor groove. The selectivity of ZT65B binding to hairpins that contained the MDR1 ICB site compared to one that did not (ICBd) was confirmed by surface‐plasmon studies, and equilibrium constants of 5×106–1×107 and 4.6×105 M−1 were obtained with ICB1, ICB5,and ICB2 respectively. ZT65B and the previously published JH37 (J. A. Henry, et al. Biochemistry 2004, 43, 12 249–12 257) serve as prototypes for the design of novel polyamides. These can be used to specifically target the subset of ubiquitous gene elements known as ICBs, and thereby affect the expression of one or a few proteins.