bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of the CT60 marker of the CTLA4 gene with systemic lupus erythematosus
Authors: Torres Belén , Aguilar Francisco , Franco Ernesto , Sánchez Elena , Sánchez‐Román Julio , Alonso Juan Jiménez , Núñez‐Roldán Antonio , Martín Javier , Francisca González‐Escribano María 
Published: July 2004

AbstractObjectiveTo investigate the possible association of the CT60A/G marker with systemic lupus erythematosus (SLE) in Spanish patients, and to identify the possible CTLA4 haplotype responsible for the association, taking into account other polymorphisms described at positions −1722T/C, −319C/T, +49A/G, and the microsatellite (AT)n in the 3′‐untranslated region (3′‐UTR) of the CTLA4 gene.MethodsGenotyping of CT60 was performed in 395 patients with SLE and 293 healthy controls using polymerase chain reaction (PCR)–restriction fragment length polymorphism analysis. Genotyping of the rest of the dimorphisms has been previously reported. Genotyping of microsatellite polymorphism (AT)n in the 3′‐UTR was performed using PCR with a fluorescence‐labeled primer.ResultsWith regard to CT60A/G, the frequency of the AA genotype was significantly decreased among the SLE patients (18.7% versus 28.3% in the control group; P = 0.003, corrected P [Pcorr] = 0.009, odds ratio [OR] = 0.58, 95% confidence interval [95% CI] 0.40–0.85). In other words, the frequency of individuals bearing the G phenotype was increased in the patient group compared with the control group (81.2% versus 71.7%; P = 0.003, Pcorr = 0.006, OR = 1.71, 95% CI 1.18–2.49). The distribution of allele frequency was also significantly different between patients and controls (P = 0.01, Pcorr = 0.02, OR [for allele G] = 1.32, 95% CI 1.06–1.65). After combining the data on the different polymorphisms, 2 neutral haplotypes were found: +49A;(AT)7;CT60A and +49G;(AT)8–19;CT60G. In addition, a susceptibility haplotype was found: +49A;(AT)>19;CT60G.ConclusionThe 3′‐UTR of the CTLA4 gene is involved in susceptibility to SLE.
Varus–valgus alignment in the progression of patellofemoral osteoarthritis
Authors: Cahue September , Dunlop Dorothy , Hayes Karen , Song Jing , Torres Leah , Sharma Leena 
Published: July 2004

AbstractObjectiveTo test the hypotheses that lateral patellofemoral (PF) osteoarthritis (OA) progression is more common than medial PF OA progression, that varus alignment increases the likelihood of medial PF OA progression, and that valgus alignment increases the likelihood of lateral PF OA progression.MethodsPatients with knee OA were recruited from the community. Inclusion criteria were definite osteophyte presence (i.e., Kellgren/Lawrence radiographic grade ≥2) in 1 or both knees and at least some difficulty with knee‐requiring activity. Varus–valgus alignment (the angle formed by the intersection of the mechanical axes of the femur and tibia) was measured on a full‐limb radiograph at baseline. To assess PF OA progression, weight‐bearing skyline views of the PF compartment were obtained at baseline and at 18‐month followup. Knees with the highest grade of PF narrowing at baseline were excluded from analysis. Logistic regression and generalized estimating equations were used; odds ratios (ORs) were adjusted for age, sex, and body mass index.ResultsLateral PF OA progression, which occurred in 120 (30%) of 397 knees, was more common than was medial PF OA progression, which occurred in 60 knees (15%). Varus (versus nonvarus) alignment increased the odds of PF OA progression isolated to the medial PF compartment (adjusted OR 1.85, 95% confidence interval [95% CI] 1.00–3.44). Valgus alignment increased the odds of PF OA progression isolated to the lateral compartment (adjusted OR 1.64, 95% CI 1.01–2.66).ConclusionLateral PF OA progression was more common than medial progression, and varus–valgus alignment influenced the likelihood of PF OA progression in a compartment‐specific manner. Interventions that address the stress imposed by alignment on the PF compartments may delay PF OA progression and should be developed.
International consensus on preliminary definitions of improvement in adult and juvenile myositis
Authors: Rider Lisa G. , Giannini Edward H. , Brunner Hermine I. , Ruperto Nicola , James‐Newton Laura , Reed Ann M. , Lachenbruch Peter A. , Miller Frederick W. 
Published: July 2004

AbstractObjectiveTo use a core set of outcome measures to develop preliminary definitions of improvement for adult and juvenile myositis as composite end points for therapeutic trials.MethodsTwenty‐nine experts in the assessment of myositis achieved consensus on 102 adult and 102 juvenile paper patient profiles as clinically improved or not improved. Two hundred twenty‐seven candidate definitions of improvement were developed using the experts' consensus ratings as a gold standard and their judgment of clinically meaningful change in the core set of measures. Seventeen additional candidate definitions of improvement were developed from classification and regression tree analysis, a data‐mining decision tree tool analysis. Six candidate definitions specifying percentage change or raw change in the core set of measures were developed using logistic regression analysis. Adult and pediatric working groups ranked the 13 top‐performing candidate definitions for face validity, clinical sensibility, and ease of use, in which the sensitivity and specificity were ≥75% in adult, pediatric, and combined data sets. Nominal group technique was used to facilitate consensus formation.ResultsThe definition of improvement (common to the adult and pediatric working groups) that ranked highest was 3 of any 6 of the core set measures improved by ≥20%, with no more than 2 worse by ≥25% (which could not include manual muscle testing to assess strength). Five and 4 additional preliminary definitions of improvement for adult and juvenile myositis, respectively, were also developed, with several definitions common to both groups. Participants also agreed to prospectively test 6 logistic regression definitions of improvement in clinical trials.ConclusionConsensus preliminary definitions of improvement were developed for adult and juvenile myositis, and these incorporate clinically meaningful change in all myositis core set measures in a composite end point. These definitions require prospective validation, but they are now proposed for use as end points in all myositis trials.
Retardation of joint damage in patients with early rheumatoid arthritis by initial aggressive treatment with disease‐modifying antirheumatic drugs: Five‐year experience from the FIN‐RACo study
Authors: Korpela Markku , Laasonen Leena , Hannonen Pekka , Kautiainen Hannu , Leirisalo‐Repo Marjatta , Hakala Markku , Paimela Leena , Blåfield Harri , Puolakka Kari , Möttönen Timo 
Published: July 2004

AbstractObjectiveTo evaluate the long‐term frequency of disease remissions and the progression of joint damage in patients with early rheumatoid arthritis (RA) who were initially randomized to 2 years of treatment with either a combination of 3 disease‐modifying antirheumatic drugs (DMARDs) or a single DMARD.MethodsIn this multicenter prospective followup study, a cohort of 195 patients with early, clinically active RA was randomly assigned to treatment with a combination of methotrexate, sulfasalazine, hydroxychloroquine, and prednisolone or with a single DMARD (initially, sulfasalazine) with or without prednisolone. After 2 years, the DMARD and prednisolone treatments became unrestricted, but were still targeted toward remission. The long‐term effectiveness was assessed by recording the frequency of remissions and the extent of joint damage seen on radiographs of the hands and feet obtained annually up to 5 years. Radiographs were assessed by the Larsen score.ResultsA total of 160 patients (78 in the combination group and 82 in the single group) completed the 5‐year extension study. At 2 years, 40% of the patients in the combination‐DMARD group and 18% in the single‐DMARD group had achieved remission (P < 0.009). At 5 years, the corresponding percentages were 28% and 22% (P not significant). The median Larsen radiologic damage scores at baseline, 2 years, and 5 years in the combination‐DMARD and single‐DMARD groups were 0 and 2 (P = 0.50), 4 and 12 (P = 0.005), and 11 and 24 (P = 0.001), respectively.ConclusionAggressive initial treatment of early RA with the combination of 3 DMARDs for the first 2 years limits the peripheral joint damage for at least 5 years. Our results confirm the earlier concept that triple therapy with combinations of DMARDs contributes to an improved long‐term radiologic outcome in patients with early and clinically active RA.
Expression and function of RANK in human monocyte chemotaxis
Authors: Mosheimer Birgit A. , Kaneider Nicole C. , Feistritzer Clemes , Sturn Daniel H. , Wiedermann Christian J. 
Published: July 2004

AbstractObjectiveRANKL, a member of the tumor necrosis factor superfamily, is a central regulator of osteoclast recruitment and activation. Whether RANKL affects monocyte locomotion in vitro via RANK and a possible signaling pathway were investigated.MethodsMonocytes were obtained from venous blood of healthy donors. Cell migration was studied by micropore filter assays. The signaling mechanisms required for RANKL‐dependent migration were tested using signaling enzyme blockers and Western blot analyses. Expression of RANK messenger RNA (mRNA) in monocytes was demonstrated by reverse transcriptase–polymerase chain reaction, and receptor expression on cell surface was investigated by fluorescence‐activated cell sorting analyses.ResultsRANKL significantly stimulated monocyte chemotaxis via activation of phosphatidylinositol 3‐kinase, phosphodiesterase, and Src kinase. The effect on migration was inhibited by osteoprotegerin, which is the decoy receptor for RANKL. Expression of RANK receptor mRNA was shown, and synthesis of RANK in monocytes was suggested by the detection of RANK immunoreactivity on the cell surface.ConclusionThese data suggest that RANK is expressed by monocytes whose activation by RANKL stimulates directed migration involving phosphatidylinositol 3‐kinase, phosphodiesterase, and Src kinases.
Lymphotoxin β–mediated stimulation of synoviocytes in rheumatoid arthritis
Authors: Braun Andrea , Takemura Seisuke , Vallejo Abbe N. , Goronzy Jörg J. , Weyand Cornelia M. 
Published: July 2004

AbstractObjectiveLymphotoxin β (LTβ), a cytokine produced by T cells and B cells, plays a central role in the normal development of lymph nodes and is critical in the formation of ectopic germinal center reactions in rheumatoid synovitis. Because resident fibroblast‐like synoviocytes (FLS) express receptors for LTβ, we examined the consequences of FLS activation by LTβ.MethodsFLS from patients with rheumatoid arthritis were isolated and examined for the expression of LTβ receptor. FLS were incubated with LTα1β2 and assayed for the production of cytokines and chemokines and the up‐regulation of adhesion molecules.ResultsExposure of FLS to recombinant LTα1β2 resulted in the production of multiple inflammatory cytokines and metalloproteinases, implicating FLS as amplifiers of the inflammatory process in the inflamed joint. Additionally, LTα1β2 was found to up‐regulate the expression of cell adhesion molecules, rendering FLS to efficient adhesion substrates for T cells. LTα1β2 also induced production of the chemokines CCL2 and CCL5, which elicited transmigration activity of T cells. Upon stimulation with LTα1β2, FLS did not acquire characteristics of follicular dendritic cells.ConclusionThese data document that FLS are involved in multiple stages of the inflammatory process, including the recruitment and retention of lymphocytes in the synovial microenvironment. We propose that the heterotypic interaction between LTβ‐producing lymphocytes and responding FLS contributes to the establishment of complex lymphoid microstructures, and that this may be one element that defines susceptibility of the synovial membrane to lymphoid organogenesis.
Dissection of class III major histocompatibility complex haplotypes associated with rheumatoid arthritis
Authors: Newton Julia L. , Harney Sinéad M. J. , Timms Andrew E. , Sims Anne‐Marie , Rockett Kirk , Darke Chris , Wordsworth B. Paul , Kwiatkowski Dominic , Brown Matthew A. 
Published: July 2004

AbstractObjectiveWe have previously identified a single‐nucleotide polymorphism (SNP) haplotype involving the lymphotoxin α (LTA) and tumor necrosis factor (TNF) loci (termed haplotype LTA–TNF2) on chromosome 6 that shows differential association with rheumatoid arthritis (RA) on HLA–DRB1*0404 and *0401 haplotypes, suggesting the presence of additional non–HLA–DRB1 RA susceptibility genes on these haplotypes. To refine this association, we performed a case–control association study using both SNPs and microsatellite markers in haplotypes matched either for HLA–DRB1*0404 or for HLA–DRB1*0401.MethodsFourteen SNPs lying between HLA–DRB1 and LTA were genotyped in 87 DRB1*04‐positive families. High‐density microsatellite typing was performed using 24 markers spanning 2,500 kb centered around the TNF gene in 305 DRB1*0401 or *0404 cases and 400 DRB1*0401 or *0404 controls. Single‐marker, 2‐marker, and 3‐marker minihaplotypes were constructed and their frequencies compared between the DRB1*0401 and DRB1*0404 matched case and control haplotypes.ResultsMarked preservation of major histocompatibility complex haplotypes was seen, with chromosomes carrying LTA–TNF2 and either DRB1*0401 or DRB1*0404 both carrying an identical SNP haplotype across the 1‐Mb region between TNF and HLA–DRB1. Using microsatellite markers, we observed two 3‐marker minihaplotypes that were significantly overrepresented in the DRB1*0404 case haplotypes (P = 0.00024 and P = 0.00097).ConclusionThe presence of a single extended SNP haplotype between LTA–TNF2 and both DRB1*0401 and DRB1*0404 is evidence against this region harboring the genetic effects in linkage disequilibrium with LTA–TNF2. Two RA‐associated haplotypes on the background of DRB1*0404 were identified in a 126‐kb region surrounding and centromeric to the TNF locus.
Dichotomous effects of complete versus partial class II major histocompatibility complex deficiency on circulating autoantibody levels in autoimmune‐prone mice
Authors: Stohl William , Xu Dong , Metzger Troy E. , Kim Kyoung Soo , Morel Laurence , Kotzin Brian L. 
Published: July 2004

AbstractObjectiveTo assess the effects of altered class II major histocompatibility complex (MHCII) expression on circulating autoantibody levels in C57BL/6 (B6) mice congenic for the Sle1 (B6.Sle1 mice) or Nba2 (B6.Nba2 mice) regions.MethodsH‐2Ab+/+ (MHCII‐intact), H‐2Ab+/– (MHCII‐intermediate), and H‐2Ab–/– (MHCII‐deficient) littermate B6.Sle1 and B6.Nba2 mice were evaluated for spleen cell phenotype, numbers of splenic Ig‐secreting cells, and serum levels of total IgM, total IgG, IgG antichromatin, IgG antihistone, and IgG anti–double‐stranded DNA (anti‐dsDNA).ResultsCompared with their MHCII‐intact littermates, MHCII‐deficient B6.Sle1 and B6.Nba2 mice developed markedly decreased circulating levels of IgG autoantibodies, along with decreased circulating levels of total IgG. In sharp contrast, MHCII‐intermediate mice developed increased circulating levels of IgG autoantibodies. This was associated with increased numbers of splenic Ig‐secreting cells and serum levels of total IgG in B6.Sle1 mice, but it occurred without concomitant increases in the numbers of splenic Ig‐secreting cells or serum total IgG levels in B6.Nba2 mice.ConclusionIn 2 clinically healthy strains of mice with a genetic proclivity for developing autoantibodies, the effects of class II MHC expression on levels of circulating IgG autoantibodies were found to be complex. In the absence of MHCII expression, circulating IgG autoantibody levels were minimal. With full MHCII expression, circulating IgG autoantibody levels were considerable. With intermediate MHCII expression, circulating IgG autoantibody levels were even greater. These last findings may help explain why heterozygosity at the H‐2 locus is associated with increased autoantibody titers and aggravated disease in certain lupus‐prone mice.
Sulfasalazine is a potent inhibitor of the reduced folate carrier: Implications for combination therapies with methotrexate in rheumatoid arthritis
Authors: Jansen Gerrit , van der Heijden Joost , Oerlemans Ruud , Lems Willem F. , Ifergan Ilan , Scheper Rik J. , Assaraf Yehuda G. , Dijkmans Ben A. C. 
Published: July 2004

AbstractObjectiveTo investigate whether interactions of sulfasalazine (SSZ) with reduced folate carrier (RFC), the dominant cell membrane transporter for natural folates and methotrexate (MTX), may limit the efficacy of combination therapy with MTX and SSZ in patients with rheumatoid arthritis.MethodsHuman RFC‐(over)expressing CEM cells of T cell origin were used to analyze the effect of SSZ on the RFC‐mediated cellular uptake of radiolabeled MTX and the natural folate leucovorin. Moreover, both cells with and those without acquired resistance to SSZ were used to assess the antiproliferative effects of MTX in combination with SSZ.ResultsTransport kinetic analyses revealed that SSZ was a potent noncompetitive inhibitor of RFC‐mediated cellular uptake of MTX and leucovorin, with mean ± SD Ki (50% inhibitory concentration) values of 36 ± 6 μM and 74 ± 7 μM, respectively. Consistent with the inhibitory interaction of SSZ with RFC, a marked loss of MTX efficacy was observed when MTX was coadministered with SSZ: up to 3.5‐fold for CEM cells in the presence of 0.25 mM of SSZ, and >400‐fold for SSZ‐resistant cells in the presence of 2.5 mM of SSZ. Importantly, along with diminished efficacy of MTX, evidence for cellular folate depletion was obtained by the demonstration of an SSZ dose–dependent decrease in leucovorin accumulation.ConclusionAt clinically relevant plasma concentrations, interactions of SSZ with RFC provide a biochemical rationale for 2 important clinical observations: 1) the onset of (sub)clinical folate deficiency during SSZ treatment, and 2) the lack of additivity/synergism of the combination of SSZ and MTX when these disease‐modifying antirheumatic drugs are administered simultaneously. Thus, when considering use of these drugs in combination therapies, the present results provide a rationale both for the use of folate supplementation and for spacing administration of these drugs over time.
Postoperative mortality following oesophagectomy and problems in reporting its rate
Authors: Jamieson G G , Mathew G , Ludemann R , Wayman J , Myers J C , Devitt P G 
Published: July 2004

Abstract

Background
There have been three previous reviews of the world literature describing postoperative mortality rate following oesophagectomy. The first documented rates in the first half of the last century, the second the period 1960–1979 and the third the interval 1980–1988. The aim of this review was to document the rate for the period 1990–2000.

Methods
Reports were sourced through PubMed and/or Medline listings.

Results
The number of papers included in the review was 312, involving 70 756 patients. The overall mortality rate was 6·7 per cent. The 30-day mortality rate was 4·9 per cent and the in-hospital mortality rate 8·8 per cent. Survival rates, where reported, were 62·7 per cent at 1 year and 27·9 per cent at 5 years.

Conclusion
Operative mortality rates following oesophagectomy have continued to fall. However, the true rate is almost certainly higher than that reported here, for a variety of reasons. The 1-year survival of patients was only reported in about a quarter of the papers. It may be a more meaningful figure than postoperative mortality rate.
Fenitrothion‐induced changes in lipids of rats
Authors: Roy Shalini , Roy Sharmila , Sharma C. B. 
Published: July 2004

AbstractThe dose‐dependent lipid accumulation caused by fenitrothion administration is associated with alteration of the ratio of various components of phospholipids and neutral lipids in various organs of rats up to 48 h. The concentration of triacylglycerol, phosphatidyl choline, phosphatidyl ethanolamine and phosphatidyl glycerol increased in liver, kidney and brain in treated rats whereas phosphatidyl serine was greatly reduced. High‐performance liquid chromatography and gas–liquid chromatography were used for quantiative analysis of phospholipids and triacylglycerol. The changes in relative composition of various lipids by fenitrothion administration may lead to malfunctioning and alteration of biological properties. Copyright © 2004 John Wiley & Sons, Ltd.
Quantitative analysis of bucillamine in blood using high‐performance liquid chromatography–mass spectrometry technique
Authors: Beaudry Francis , Proulx Dave , Furtado Milton 
Published: July 2004

AbstractA fast and sensitive method has been developed and validated for the determination of bucillamine in human blood by derivatizing the free sulfhydryl groups with isobutyl acrylate (IA), by APCI‐LC/MS/MS. The collected blood sample was immediately mixed with a mixture of IA and 0.05 m Tris(hydroxymethyl)aminomethane hydrochloride (Tris–HCl) buffer, pH 9.2, to stabilize the sulfyhydryl moieties. The derivatized samples were then extracted by protein precipitation, evaporated, reconstituted and injected using an LC‐APCI/MS/MS instrument. Separation was achieved using a C18 analytical column and a gradient mobile phase within a chromatographic run time of 5 min. A quadratic (weighted 1/concentration2) relationship was observed during validation over a concentration range of 0.4–40 µg/mL with a correlation value of r ≥ 0.9966. The inter‐batch precision and accuracy at low, medium and high concentrations were 8.1, 8.4 and 7.3%; 113.3, 104.9 and 103.9%, respectively, and the intra‐batch precision and accuracy at low, medium and high concentrations were 7.7, 5.4 and 2.7%; 105.1, 111.9 and 113.2%, respectively. Copyright © 2004 John Wiley & Sons, Ltd.
Sequence alignment on the Cray MTA‐2
Authors: Bokhari Shahid H. , Sauer Jon R. 
Published: July 2004

AbstractSeveral variants of standard algorithms for DNA sequence alignment have been implemented on the Cray Multithreaded Architecture‐2 (MTA‐2). We describe the architecture of the MTA‐2 and discuss how its hardware and software enable efficient implementation of parallel algorithms with little or no regard for issues of partitioning, mapping or scheduling. We describe how we ported variants of the naive algorithm for exact alignment and the dynamic programming algorithm for approximate alignment to the MTA‐2 and provide detailed performance measurements. It is shown that, for the dynamic programming algorithm, the use of the MTA's ‘Full/Empty’ synchronization bits leads to almost perfect speedup for large problems on one to eight processors. These results illustrate the versatility of the MTA's architecture and demonstrate its potential for providing a high‐productivity platform for parallel processing. Copyright © 2004 John Wiley & Sons, Ltd.
Using hybrid alignment for iterative sequence database searches
Authors: Li Yuheng , Lauria Mario , Bundschuh Ralf 
Published: July 2004

AbstractProgressive sequence model refinement by means of iterative searches is an effective technique for high sensitivity database searches and is currently employed in popular tools such as PSI‐BLAST and SAM. Recently, a novel alignment algorithm has been proposed that offers features expected to improve the sensitivity of such iterative approaches, specifically a well‐characterized theory of its statistics even in the presence of position‐specific gap costs. Here, we demonstrate that the new hybrid alignment algorithm is ready to be used as the alignment core of PSI‐BLAST. In addition, we evaluate the accuracy of two proposed approaches to edge effect correction in short sequence alignment statistics that turns out to be one of the crucial issues in developing a hybrid‐alignment based version of PSI‐BLAST. Copyright © 2004 John Wiley & Sons, Ltd.