bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pervaporation separation of a water–ethanol mixture by PSF–PEG membrane
Authors: Hsu Ching‐Shan , Liou Rey May , Chen Shih‐Hsiung , Hung Mu‐Ya , Tsia Hui‐An , Lai Juin‐Yih 
Published: January 2003

AbstractFor dehydrating a water–ethanol mixture by pervaporation, a polysulfone–And poly(ethylene glycol)(PSF–PEG) membrane was prepared. The separation performance of water and ethanol was found to strongly depend on the diffusion selectivity of permeates. On the other hand, the solubility selectivity of water to ethanol showed only minor change with an increasing PEG composition of the PSF–PEG membrane. This study found that the PEG content in a PSF–PEG membrane showed mobility enhancement of pervaporation properties and that the diffusion difference of permeates increased with increasing PEG content. The effect of PEG content on separation performance was a result of the improvement of the permeate diffusion properties of the PSF/PEG membrane. The diffusion difference in the membrane, not the solubility of water–ethanol in the membrane, was the dominant factor for the separation. Suitable PEG content in PSF/PEG membranes can prepare a high‐performance pervaporation membrane. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 87: 2158–2164, 2003
Pervaporation properties of aromatic/nonaromatic hydrocarbons of crosslinked membranes of copolymers based on diethyl vinylbenzylphosphonate
Authors: Wang Yong , Hirakawa Satoshi , Tanaka Kazuhiro , Kita Hidetoshi , Okamoto Ken‐ichi 
Published: January 2003

AbstractCopoly(diethyl vinylbenzylphosphonate/hydroxyethyl methacrylate) [copoly(VBP–HEMA)] and copoly(diethyl vinylbenzylphosphonate/vinylbenzyl chloride) [copoly(VBP–VBC)] were prepared and their membranes crosslinked by a reaction of ethylene glycol diglycidyl ether and ethylene diamine with, respectively, hydroxyl and methylene chloride groups in their side chains. Pervaporation (PV) and sorption of benzene–n‐hexane (Bz–Hx), benzene–cyclohexane (Bz–Cx), and toluene–n‐octane (Tol–n‐Ot) mixtures were investigated. The membranes were in a rubbery state and preferentially permeable to aromatics. They had higher specific permeation flux and a lower PV separation factor compared with the crosslinked membranes of methacrylate copolymers with analogous pendant groups. They displayed better PV performance for Tol–n‐Ot. Sorption isotherms of Bz–Hx mixtures were represented by the Flory–Rehner model. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 87: 2177–2185, 2003
Adalimumab, a fully human anti–tumor necrosis factor α monoclonal antibody, for the treatment of rheumatoid arthritis in patients taking concomitant methotrexate: The ARMADA trial
Authors: Weinblatt Michael E. , Keystone Edward C. , Furst Daniel E. , Moreland Larry W. , Weisman Michael H. , Birbara Charles A. , Teoh Leah A. , Fischkoff Steven A. , Chartash Elliot K. 
Published: January 2003

AbstractObjectiveTo evaluate the efficacy and safety of adalimumab (D2E7), a fully human monoclonal tumor necrosis factor α antibody, in combination with methotrexate (MTX) in patients with active rheumatoid arthritis (RA) despite treatment with MTX.MethodsIn a 24‐week, randomized, double‐blind, placebo‐controlled study, 271 patients with active RA were randomly assigned to receive injections of adalimumab (20 mg, 40 mg, or 80 mg subcutaneously) or placebo every other week while continuing to take their long‐term stable dosage of MTX. The primary efficacy end point was the American College of Rheumatology criteria for 20% improvement (ACR20) at 24 weeks.ResultsAn ACR20 response at week 24 was achieved by a significantly greater proportion of patients in the 20‐mg, 40‐mg, and 80‐mg adalimumab plus MTX groups (47.8%, 67.2%, and 65.8%, respectively) than in the placebo plus MTX group (14.5%) (P < 0.001). ACR50 response rates with the 20‐mg, 40‐mg, and 80‐mg adalimumab dosages (31.9%, 55.2%, and 42.5%, respectively) were significantly greater than that with placebo (8.1%) (P = 0.003, P < 0.001, and P < 0.001, respectively). The 40‐mg and 80‐mg doses of adalimumab were associated with an ACR70 response (26.9% and 19.2%, respectively) that was statistically significantly greater than that with placebo (4.8%) (P < 0.001 and P = 0.020). Responses were rapid, with the greatest proportion of adalimumab‐treated patients achieving an ACR20 response at the first scheduled visit (week 1). Adalimumab was safe and well tolerated; comparable numbers of adalimumab‐treated patients and placebo‐treated patients reported adverse events.ConclusionThe addition of adalimumab at a dosage of 20 mg, 40 mg, or 80 mg administered subcutaneously every other week to long‐term MTX therapy in patients with active RA provided significant, rapid, and sustained improvement in disease activity over 24 weeks compared with MTX plus placebo.
Integrin‐mediated adhesion of human articular chondrocytes to cartilage
Authors: Kurtis Melissa S. , Schmidt Tannin A. , Bugbee William D. , Loeser Richard F. , Sah Robert L. 
Published: January 2003

AbstractObjectiveTo determine 1) the kinetics and strength of adhesion of human articular chondrocytes to a cut cartilage surface, and 2) the role of specific integrins in mediating such adhesion, using an in vitro model.MethodsHuman articular chondrocytes isolated from cadaveric donors (mean ± SD age 38 ± 13 years) were cultured in high‐density or low‐density monolayer. Following release from culture with trypsin and a 2–2.5‐hour recovery period, chondrocytes were analyzed either for adhesion to cartilage or for integrin expression by flow cytometry.ResultsFollowing culture in monolayer, adhesion of chondrocytes to cartilage increased with time, from 6–16% at 10 minutes to a maximum of 59–82% at 80–320 minutes. After 80 minutes of adhesion, the resistance of cells to flow‐induced shear stress (50% detachment) was ∼21 Pa. Chondrocyte adhesion to cartilage decreased with pretreatment of cells with monoclonal antibodies that bound to and blocked certain integrins. After an 80‐minute incubation time, adhesion of chondrocytes cultured in high‐density monolayer decreased from the value of IgG1‐treated controls (55%) with blocking of the β1 integrin subunit (to 23%) or with blocking of α5β1 (to 36%). Following expansion of chondrocytes in low‐density monolayer, the mechanisms of adhesion to cartilage were generally similar. After an 80‐minute incubation time, adhesion of chondrocytes cultured in low‐density monolayer decreased from the value of IgG1‐treated controls (62%) with blocking of the β1 integrin subunit (to 30%) or with blocking of α5β1 (to 44%). Additionally, adhesion of these cells decreased to 46% by blocking of αvβ5, with a similar trend in effect for chondrocytes cultured in high‐density monolayer. Blocking of the α1 or α3 integrin subunits or αvβ3 had no detectable effect on adhesion, even though these receptors were detected by flow cytometry.ConclusionUnder the culture and seeding conditions studied, β1, α5β1, and αvβ5 integrins mediate human chondrocyte adhesion to cartilage. These chondrocyte integrins have a potential role in the initial adhesion and retention of chondrocytes at a cartilage defect site following clinical procedures of chondrocyte transplantation.
Survival in rheumatoid arthritis: A population‐based analysis of trends over 40 years
Authors: Gabriel Sherine E. , Crowson Cynthia S. , Kremers Hilal Maradit , Doran Michele F. , Turesson Carl , O'Fallon W. Michael , Matteson Eric L. 
Published: January 2003

AbstractObjectiveTo evaluate trends in and risk factors for mortality among patients with rheumatoid arthritis (RA) over a 40‐year period.MethodsA population‐based inception cohort was assembled from among all Rochester, Minnesota residents ages ≥18 years who were first diagnosed with RA (fulfilling the 1987 American College of Rheumatology criteria for RA) between January 1, 1955 and December 31, 1994. Patients were followed up longitudinally through their entire medical records (including all inpatient and outpatient care by any provider) until death or migration from the county. Survival was described using the Kaplan‐Meier method. Observed and expected survival were compared using the log‐rank test, and standardized mortality ratios (SMRs) with expected survival were based on the sex and age of the study population and death rates from the Minnesota life tables. Cox proportional hazards models were used to estimate the influence of extraarticular manifestations and comorbidities, controlling for age, sex, body mass index (BMI), smoking, and rheumatoid factor positivity.ResultsSurvival in this RA cohort was significantly lower than that expected in the population (P < 0.001) over the entire time period. Patients with RA were at significantly higher risk of death, with an SMR of 1.27 (95% confidence interval 1.13–1.41). Excess mortality among women was more pronounced than among men, with SMRs of 1.41 and 1.08, respectively. Presence of ≥1 extraarticular manifestation was the strongest predictor of mortality after adjusting for age, sex, BMI, smoking, and rheumatoid factor positivity.ConclusionSurvival in RA patients is significantly lower than expected. The strongest predictors of survival appear to be those related to RA disease complications, specifically, extraarticular manifestations of the disease and comorbidities. More attention should be paid to mortality as an outcome measure in RA.
Induction of matrix metalloproteinase 1 gene expression is regulated by inflammation‐responsive transcription factor SAF‐1 in osteoarthritis
Authors: Ray Alpana , Kuroki Keiichi , Cook James L. , Bal B. Sonny , Kenter Keith , Aust Gabriela , Ray Bimal K. 
Published: January 2003

AbstractObjectiveTo identify specific transcription factors that are activated in the cartilage tissue of osteoarthritis (OA) patients and are involved in the expression of matrix metalloproteinase 1 (MMP‐1).MethodsDNase I footprint and electrophoretic mobility shift assays were performed to identify active elements of the MMP1 promoter and the transcription factors that interact with it. The relative abundance of the involved transcription factor in the cartilage was determined by immunohistochemical analysis. The role of serum amyloid A–activating factor 1 (SAF‐1) in MMP‐1 expression was assessed by transient transfection assay with plasmids containing either a functional or an antisense SAF‐1 complementary DNA.ResultsA novel promoter element was detected in the human MMP1 gene, and the inflammation‐responsive transcription factor SAF‐1 was found to interact with it. SAF‐1 activity was detected in the chondrocytes of OA cartilage, where most of the cells stained positive for SAF‐1. Overexpression of SAF‐1 in OA chondrocytes increased the expression of the MMP1 promoter, and interference of endogenous SAF‐1 activity by antisense SAF‐1 messenger RNA inhibited interleukin‐1–mediated MMP1 promoter activity.ConclusionThe results indicate that SAF‐1 is involved in the regulation of MMP1 gene expression and it is highly abundant in the articular cartilage chondrocytes of OA patients. The data also demonstrate that control of SAF‐1 activity can suppress induced expression of MMP‐1. Conceivably, SAF‐1 could be a potential therapeutic target to control the overexpression of MMP‐1 associated with the pathogenesis of OA.
Rapid induction of peroxisome proliferator–activated receptor γ expression in human monocytes by monosodium urate monohydrate crystals
Authors: Akahoshi Tohru , Namai Rie , Murakami Yousuke , Watanabe Megumi , Matsui Toshimichi , Nishimura Akito , Kitasato Hidero , Kameya Toru , Kondo Hirobumi 
Published: January 2003

AbstractObjectivePeroxisome proliferator–activated receptor γ (PPARγ) is a member of the nuclear hormone receptor superfamily and functions as a key regulator of lipid and glucose metabolism, atherosclerosis, and inflammatory responses. This study was undertaken to evaluate the biologic role of PPARγ in self‐limiting episodes of acute gouty arthritis. To do this, we investigated PPARγ expression by monosodium urate monohydrate (MSU) crystal–stimulated monocytes, and we studied the effects of PPARγ ligands on crystal‐induced acute inflammation.MethodsPPARγ expression by MSU crystal–stimulated human peripheral blood mononuclear cells was determined by reverse transcription–polymerase chain reaction and immunostaining. Expression of CD36 on monocytes was detected by flow cytometric analysis. The effects of PPARγ ligands on in vitro crystal‐induced cytokine production and on in vivo cellular infiltration during crystal‐induced acute inflammation were also investigated.ResultsMSU crystals rapidly and selectively induced PPARγ expression by monocytes. Gene expression was detected as early as 2 hours, and maximum expression was observed at 4 hours after stimulation. The induced PPARγ was functional, since a PPARγ ligand was able to up‐regulate CD36 expression on monocytes. A natural ligand of PPARγ, 15‐deoxy‐Δ12,14‐prostaglandin J2 (15deoxy‐PGJ2), significantly reduced the crystal‐induced production of cytokines by monocytes. Indomethacin inhibited cytokine production only at high concentrations, and an antidiabetic thiazolidinedione (troglitazone) failed to exert significant effects. Administration of troglitazone and 15deoxy‐PGJ2 significantly prevented cellular accumulation in a mouse air‐pouch model of MSU crystal–induced acute inflammation.ConclusionRapid induction of PPARγ expression on monocytes by MSU crystals may contribute, at least in part, to the spontaneous resolution of acute attacks of gout.
Long‐term efficacy and safety of etanercept in children with polyarticular‐course juvenile rheumatoid arthritis: Interim results from an ongoing multicenter, open‐label, extended‐treatment trial
Authors: Lovell Daniel J. , Giannini Edward H. , Reiff Andreas , Jones Olcay Y. , Schneider Rayfel , Olson Judyann C. , Stein Leonard D. , Gedalia Abraham , Ilowite Norman T. , Wallace Carol A. , Lange Mary , Finck Barbara K. , Burge Daniel J. ,   for the Pediatric Rheumatology Collaborative Study Group
Published: January 2003

AbstractObjectiveTo evaluate the long‐term efficacy and safety of etanercept in children with juvenile rheumatoid arthritis (JRA) participating in an ongoing multicenter, open‐label, extended‐treatment trial. All patients had been participants in an initial randomized efficacy and safety trial of etanercept.MethodsEtanercept was administered at a dosage of 0.4 mg/kg (maximum 25 mg) subcutaneously twice each week. Safety and efficacy evaluations were performed every 3–4 months. The JRA 30% definition of improvement (DOI) was defined as improvement of ≥30% in at least 3 of 6 response variables used to assess disease activity, with no more than 1 variable worsening by more than 30%.ResultsAt the time of analysis, 48 of the 58 patients (83%) were still enrolled in the study; 43 of them (74%) had completed 2 years of treatment. Of these 43 patients, 81% met the JRA 30% DOI, 79% met the JRA 50% DOI, and 67% met the JRA 70% DOI. Ten children started low‐dose methotrexate after year 1. Of the 32 children taking prednisone, the dosage was decreased to <5 mg/day in 26 (81%). Two children had serious infections (varicella with aseptic meningitis in one and complicated sepsis in the other). In general, adverse events were of the types seen in a general pediatric patient population.ConclusionChildren with severe, longstanding, methotrexate‐resistant polyarticular JRA demonstrated sustained clinical improvement with >2 years of continuous etanercept treatment. Etanercept was generally well‐tolerated. There were no increases in the rates of adverse events over time. However, children taking etanercept should be monitored closely for infections.
Tachykinin expression in cartilage and function in human articular chondrocyte mechanotransduction
Authors: Millward‐Sadler S. J. , Mackenzie A. , Wright M. O. , Lee H.‐S. , Elliot K. , Gerrard L. , Fiskerstrand C. E. , Salter D. M. , Quinn J. P. 
Published: January 2003

AbstractObjectiveTo assess whether substance P and the corresponding neurokinin 1 (NK1) receptor are expressed in human articular cartilage, and whether these molecules have a role in chondrocyte mechanotransduction.MethodsTransgenic studies, immunohistochemistry, Western blotting, and reverse transcriptase–polymerase chain reaction were used to assess the expression of the preprotachykinin (PPT) gene, substance P, and NK1 in developing mice, in adult human articular cartilage, and in human chondrocytes in culture. Chondrocytes obtained from PPT knockout mice and human articular chondrocytes were mechanically stimulated in the presence or absence of inhibitors of substance P signaling, and cell membrane potentials or relative levels of aggrecan messenger RNA (mRNA) were measured.ResultsReplacing a region of the PPT gene transcriptional site that contains a dominant repressor of the proximal promoter activity with the constitutive minimal promoter of the human β‐globin promoter allowed expression of a marker gene in areas of chondrogenesis during mouse development and in adult chondrocytes grown in culture. Adult human articular chondrocytes expressed endogenous PPT mRNA, substance P, and the corresponding NK1 receptor in vivo and in vitro. Blockade of substance P signaling by a chemical antagonist to the NK1 receptor inhibited chondrocyte responses to mechanical stimulation.ConclusionSubstance P is expressed in human articular cartilage and is involved in chondrocyte mechanotransduction via the NK1 receptor in an autocrine and paracrine manner. This suggests that substance P and the NK1 receptor have roles in the maintenance of articular cartilage structure and function that were previously unrecognized.
Adenosine A2A or A3 receptors are required for inhibition of inflammation by methotrexate and its analog MX‐68
Authors: Montesinos M. Carmen , Desai Avani , Delano Dave , Chen Jiang‐Fan , Fink J. Stephen , Jacobson Marlene A. , Cronstein Bruce N. 
Published: January 2003

AbstractObjectiveLow‐dose weekly methotrexate therapy remains a mainstay in the treatment of inflammatory arthritis. Results of previous studies demonstrated that adenosine, acting at one or more of its receptors, mediates the antiinflammatory effects of methotrexate in animal models of both acute and chronic inflammation. We therefore sought to establish which receptor(s) is involved in the modulation of acute inflammation by methotrexate and its nonpolyglutamated analog MX‐68 (N‐[[4‐[(2,4‐diaminopteridin‐6‐yl)methyl]‐3,4‐dihydro‐2H‐1,4‐benzothiazin‐7‐yl]‐carbonyl]‐L‐homoglutamic acid).MethodsWe studied the effects of low‐dose methotrexate (0.75 mg/kg intraperitoneally [IP] every week for 5 weeks), MX‐68 (2 mg/kg IP 2 days and 1 hour before induction of inflammation), dexamethasone (1.5 mg/kg IP 1 hour before induction of inflammation), or vehicle control on acute inflammation in an air‐pouch model in A2A and A3 receptor knockout mice.ResultsLow‐dose weekly methotrexate treatment increased the adenosine concentration in the exudates of all mice studied and reduced leukocyte and tumor necrosis factor α accumulation in the exudates of wild‐type mice, but not in those of A2A or A3 receptor knockout mice. Dexamethasone, an agent that suppresses inflammation by a different mechanism, was equally effective at suppressing leukocyte accumulation in A2A knockout, A3 knockout, and wild‐type mice, indicating that the lack of response was specific for methotrexate and MX‐68.ConclusionThese findings confirm that adenosine, acting at A2A and A3 receptors, is a potent regulator of inflammation. Moreover, these results provide strong evidence that adenosine, acting at either or both of these receptors, mediates the antiinflammatory effects of methotrexate and its analog MX‐68.
Laser‐mediated microdissection facilitates analysis of area‐specific gene expression in rheumatoid synovium
Authors: Judex M. , Neumann E. , Lechner S. , Dietmaier W. , Ballhorn W. , Grifka J. , Gay S. , Schölmerich J. , Kullmann F. , Müller‐Ladner U. 
Published: January 2003

AbstractObjectiveCurrent approaches to analyzing gene expression in rheumatoid arthritis (RA) synovium are based on RNA isolated either from cultured synovial cells or from synovial biopsy specimens. This strategy does not, in general, allow distinction of specific gene expression between cells originating from different synovial areas, due to potential mixture of expression profiles. Therefore, we established the combination of laser‐mediated microdissection (LMM) and differential display to analyze profiles of gene expression in histologically defined areas of rheumatoid synovium. The present study was undertaken to establish parameters for this technique and assess its usefulness for gene expression analysis.MethodsCryosections derived from RA synovial tissues were used to obtain cell samples from synovial lining versus sublining, using a microbeam laser microscope. RNA was isolated and analyzed by nested RNA arbitrarily primed–polymerase chain reaction (RAP‐PCR) for differential display fingerprinting. Differentially expressed bands were cut out, and PCR products were eluted, cloned, and sequenced. Differential expression of identified sequences was confirmed by in situ hybridization and immunohistochemistry analysis.ResultsMicrodissected sections of RA synovial tissue containing ∼600 cells yielded enough RNA to produce a reproducible RNA fingerprint pattern. Several genes could be identified as being expressed differentially between the synovial lining and the sublining, and their expression could be confirmed at the messenger RNA and protein levels.ConclusionThe combination of LMM and RAP‐PCR presents a valuable tool to obtain novel insights into the area‐dependent differential regulation of gene expression in RA synovium. Both known and previously unknown genes were revealed with this technique. This study is the first to demonstrate the potential of this analytic strategy in the investigation of a nonmalignant, multifactorial, inflammatory disease.
The effect of HLA–DR on susceptibility to rheumatoid arthritis is influenced by the associated lymphotoxin α–tumor necrosis factor haplotype
Authors: Newton Julia , Brown Matthew A. , Milicic Anita , Ackerman Hans , Darke Chris , Wilson Jonathan N. , Wordsworth B. Paul , Kwiatkowski Dominic 
Published: January 2003

AbstractObjectiveHLA–DRB1, a major genetic determinant of susceptibility to rheumatoid arthritis (RA), is located within 1,000 kb of the gene encoding tumor necrosis factor (TNF). Because certain HLA–DRB1*04 subtypes increase susceptibility to RA, investigation of the role of the TNF gene is complicated by linkage disequilibrium (LD) between TNF and DRB1 alleles. By adequately controlling for this LD, we aimed to investigate the presence of additional major histocompatibility complex (MHC) susceptibility genes.MethodsWe identified 274 HLA–DRB1*04–positive cases of RA and 271 HLA–DRB1*04–positive population controls. Each subject was typed for 6 single‐nucleotide polymorphisms within a 4.5‐kb region encompassing TNF and lymphotoxin α (LTA). LTA–TNF haplotypes in these unrelated individuals were determined using a combination of family data and the PHASE software program.ResultsSignificant differences in LTA–TNF haplotype frequencies were observed between different subtypes of HLA–DRB1*04. The LTA–TNF haplotypes observed were very restricted, with only 4 haplotypes constituting 81% of all haplotypes present. Among individuals carrying DRB1*0401, the LTA–TNF 2 haplotype was significantly underrepresented in cases compared with controls (odds ratio 0.5 [95% confidence interval 0.3–0.8], P = 0.007), while in those with DRB1*0404, the opposite effect was observed (P = 0.007).ConclusionThese findings suggest that the MHC contains genetic elements outside the LTA–TNF region that modify the effect of HLA–DRB1 on susceptibility to RA.