bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mapping the HLA association in Behçet's disease: A role for tumor necrosis factor polymorphisms?
Authors: Ahmad Tariq , Wallace Graham R. , James Teifi , Neville Matt , Bunce Mike , Mulcahy‐Hawes Kim , Armuzzi Alessandro , Crawshaw Jonathan , Fortune Farida , Walton Robert , Stanford Miles R. , Welsh Ken I. , Marshall Sara E. , Jewell Derek P. 
Published: March 2003

AbstractObjectiveExperimental evidence suggests that inappropriate regulation of tumor necrosis factor α (TNFα) may play a role in the pathogenesis of Behçet's disease (BD). This is supported by recent reports highlighting the efficacy of anti‐TNFα agents in the treatment of this disease. The TNF gene is encoded in the class III region of the HLA complex adjacent to HLA–B. This genetic proximity to a gene that is already widely implicated in disease susceptibility led us to investigate the association between TNF promoter polymorphisms and susceptibility to BD.MethodsWe studied 133 UK white Caucasoid patients with BD and 354 healthy controls. We attempted to dissect the contribution of individual polymorphisms in this gene‐dense region by linkage disequilibrium mapping across 6 adjacent genes.ResultsWe report a novel association with the TNF promoter allele TNF‐1031C. Subsequent analysis identified 2 extended HLA haplotypes associated with BD. One of them contained the previously recognized susceptibility gene HLA–B*51, while the other was defined by HLA–B*5701. Both of these haplotypes contained the TNF promoter polymorphism −1031C, an allele that was associated with disease even in individuals who did not carry either HLA–B*51 or HLA–B*5701.ConclusionThe TNF‐1031C allele is independently associated with susceptibility to BD in Caucasoid patients. Further studies will be required to determine the functional effects of this polymorphism, its influence in disease pathogenesis, and its role in other ethnic groups.
An index of the three core data set patient questionnaire measures distinguishes efficacy of active treatment from that of placebo as effectively as the American College of Rheumatology 20% response criteria (ACR20) or the Disease Activity Score (DAS) in a rheumatoid arthritis clinical trial
Authors: Pincus T. , Strand V. , Koch G. , Amara I. , Crawford B. , Wolfe F. , Cohen S. , Felson D. 
Published: March 2003

AbstractObjectiveTo evaluate the capacity of a pooled index of only the 3 patient self‐report questionnaire measures among the 7 American College of Rheumatology (ACR) core data set (Core Data Set) measures to distinguish efficacy of active treatment of rheumatoid arthritis (RA) with leflunomide or methotrexate versus placebo in a randomized, controlled clinical trial, and to compare the results with those obtained using the ACR 20% response criteria (ACR20), Disease Activity Score (DAS), and other pooled indices.MethodsThe 7 ACR Core Data Set measures of 1) joint swelling, 2) joint tenderness, 3) physician global assessment, 4) erythrocyte sedimentation rate (ESR), 5) functional disability, 6) pain, and 7) patient global assessment were combined into the following 5 pooled indices: “All Core Data Set” (all 7 measures), “Assessor Only” (measures 1–3), “Assessor + ESR” (measures 1–4), “Patient Only” (measures 5–7), and “Patient + ESR” (measures 4–7). The capacity of each of these 5 indices to detect differences between active treatment and placebo treatment was compared with that of the ACR20 and the DAS using 4 different analytic methods, each of which presented advantages and limitations. Agreement of the indices with one another and with the ACR20 and the DAS was analyzed according to pairwise kappa statistics and Z scores in multivariate logistic regression models.ResultsEach of the 5 indices, including “Patient Only,” had a similar capacity to detect greater efficacy of leflunomide and methotrexate versus placebo in this clinical trial, according to each of 4 methods, at similar levels of statistical and clinical significance.ConclusionA pooled index of patient self‐report questionnaire Core Data Set measures appears to be as informative as ACR20 responses, DAS scores, and pooled indices of all and assessor‐derived Core Data Set measures for distinguishing between active treatment and placebo treatment in this RA clinical trial.
Heterogeneity of response of rheumatoid synovium cell subsets to interleukin‐18 in relation to differential interleukin‐18 receptor expression
Authors: Kawashima Masanori , Miossec Pierre 
Published: March 2003

AbstractObjectiveTo examine the differential response of rheumatoid arthritis (RA) synovium cell subsets to interleukin‐18 (IL‐18), the effect of IL‐18 on Th1‐cytokine production, and the regulation of IL‐18 by IL‐18 binding protein (IL‐18BP).MethodsRA fibroblast‐like synoviocytes were stimulated with IL‐1β, IL‐12, and IL‐18, and levels of IL‐6 were measured by enzyme‐linked immunosorbent assay (ELISA). Expression of IL‐18 receptor α and β chains (IL‐18Rα and IL‐18Rβ, respectively), interferon‐γ (IFNγ), and IL‐17 messenger RNA (mRNA) by peripheral blood mononuclear cells, by total RA synovium cells containing T cells obtained after collagenase digestion, and by RA fibroblast‐like synoviocytes was determined by reverse transcription–polymerase chain reaction. Levels of IFNγ were measured by ELISA.ResultsIL‐1β and, less effectively, IL‐12 could induce RA fibroblast‐like synoviocytes to produce IL‐6, but IL‐18 failed to have an effect. Although IL‐18Rα mRNA was constitutively expressed by RA fibroblast‐like synoviocytes, IL‐18Rβ could not be detected, either with or without stimulation with IL‐1 or IL‐12. Total RA synovium cells containing T cells showed a strong expression of both IL‐18Rα and IL‐18Rβ mRNA, and only IL‐18Rβ was up‐regulated by IL‐12. The combination of IL‐12 and IL‐18 synergistically up‐regulated IFNγ mRNA expression by total RA synovium cells containing T cells, but down‐regulated that of IL‐17. IL‐12–induced IFNγ production by total RA synovium cells containing T cells was increased by additional IL‐18 and decreased by IL‐18BP.ConclusionThese results indicate that IL‐18 plays an important role in RA inflammation and joint destruction via T cells and macrophages, but it does not have a direct effect on fibroblast‐like synoviocytes. IL‐18BP may be a tool for RA therapy because of its ability to neutralize endogenous IL‐18.
Down‐regulation of Th1‐mediated pathology in experimental arthritis by stimulation of the Th2 arm of the immune response
Authors: Mauri Claudia , Feldmann Marc , Williams Richard O. 
Published: March 2003

AbstractObjectiveTo assess whether systemic administration of recombinant interferon‐γ (rIFNγ), a proinflammatory cytokine that influences the differentiation of naive T cells into Th1 cells, promotes the induction of arthritis in DBA/1 mice immunized with type II collagen (CII) in Freund's incomplete adjuvant (IFA) and to determine the antiarthritic effect of treatment with CII in IFA.MethodsDBA/1 mice were immunized with CII in IFA and injected intraperitoneally with rIFNγ (8,000 units/mouse/day) or with recombinant interleukin‐12 (rIL‐12; 100 ng/mouse/day). In another experiment, mice were immunized with CII in Freund's complete adjuvant (CFA) and treated with a single dose of CII in IFA on the day of immunization or on the day of disease onset. Mice were monitored to assess the effect of the treatment on the severity of disease. Th1/Th2 cytokines and anti‐CII antibodies were measured by enzyme‐linked immunosorbent assay.ResultsThe administration of rIL‐12 or rIFNγ to mice immunized with CII in IFA restored the Th1 response and resulted in the development of arthritis. We then determined whether immunization with CII in IFA had the capacity to prevent and/or ameliorate collagen‐induced arthritis. A single intraperitoneal injection of CII in IFA prevented arthritis when given at the time of immunization with CII in CFA and reduced disease severity when given at the time of arthritis onset. The administration of CII in IFA resulted in a profound down‐regulation of IFNγ production and an up‐regulation of IL‐10 in cultures of draining lymph node cells.ConclusionThese findings demonstrate that it is possible to deflect an ongoing pathogenic Th1 response to an antigen by reimmunization of the same antigen with a Th2‐polarizing adjuvant.
Leonard Trask: The wonderful invalid: The first American description of ankylosing spondylitis
Authors: Jayson Malcolm I. V. 
Published: March 2003

AbstractThis report describes the first published clinical account of a case of ankylosing spondylitis in the United States. The patient progressively developed very severe kyphosis with resultant severe disability. The condition apparently started after an accident, and the report has interesting medicolegal implications.
Selective stimulation of collagen synthesis in the presence of costimulatory insulin signaling by connective tissue growth factor in scleroderma fibroblasts
Authors: Gore‐Hyer Elizabeth , Pannu Jaspreet , Smith Edwin A. , Grotendorst Gary , Trojanowska Maria 
Published: March 2003

AbstractObjectiveTo examine the mechanism of collagen induction by connective tissue growth factor (CTGF), a profibrotic cytokine overexpressed in the skin of patients with systemic sclerosis (SSc).MethodsDermal fibroblasts from 7 SSc patients and 7 matched healthy adult donors were stimulated with CTGF in the presence or absence of the culture‐medium supplement, insulin–transferrin–selenium (ITS). Expression of collagen protein was analyzed by a 3H‐proline incorporation assay. To identify the signaling pathways mediating CTGF induction of collagen, pharmacologic inhibitors were used, including rottlerin, a protein kinase Cδ (PKCδ) inhibitor.ResultsCollagen levels in both SSc and normal fibroblasts were increased after treatment with transforming growth factor β in serum‐free medium, whereas no stimulation was observed following addition of CTGF. In the presence of ITS, CTGF (2.5 ng/ml) potently stimulated collagenous protein levels in SSc cell lines (n = 5); however, CTGF was not stimulatory in the majority of normal fibroblasts (n = 6). ITS alone induced collagen levels in normal fibroblasts to the levels observed in SSc skin fibroblasts, thereby diminishing the hallmark difference in basal collagen levels in these cell types. Insulin was the ITS component responsible for promoting the basal and CTGF stimulation of collagenous proteins. Rottlerin, the PKCδ inhibitor, down‐regulated collagen synthesis in normal and SSc fibroblasts cultured in ITS, and inhibited the stimulatory effects of CTGF in cooperation with insulin or of insulin (500 ng/ml) alone.ConclusionIncreased responsiveness of SSc fibroblasts to CTGF‐mediated collagen synthesis requires the costimulatory activation of insulin signaling pathways to induce matrix production. Blockade of this effect via rottlerin may suggest that PKCδ is a downstream signaling molecule necessary for CTGF stimulation of collagen synthesis.
Specific increase in enzymatic activity of adenosine deaminase 1 in rheumatoid synovial fibroblasts
Authors: Nakamachi Yuji , Koshiba Masahiro , Nakazawa Takashi , Hatachi Saori , Saura Ryuichi , Kurosaka Masahiro , Kusaka Hideaki , Kumagai Shunichi 
Published: March 2003

AbstractObjectiveAdenosine deaminase (ADA; EC 3.5.4.4) activity is elevated in the synovial fluid (SF) of patients with rheumatoid arthritis (RA). Since the antiinflammatory effect of methotrexate is reportedly associated with increased levels of extracellular adenosine, the present study was undertaken to clarify the role of 2 ADA isozymes, ADA1 and ADA2, in the pathogenesis of RA.MethodsThe activities of ADA1 and ADA2 were measured in SF from RA and osteoarthritis (OA) patients, in sera from RA patients, and in lysates prepared from mononuclear and polymorphonuclear cells from SF from RA patients, peripheral blood from RA patients, and fibroblast‐like synoviocytes (FLS) from RA and OA patients. Also measured were the effects of proinflammatory cytokines on ADA1 activity and ADA messenger RNA (mRNA) expression in RA FLS, as determined using real‐time polymerase chain reaction. The adenosine concentration in RA SF was measured by radioimmunoassay.ResultsThe adenosine concentration in RA SF ranged from 0.027 μM to 0.508 μM (mean ± SD 0.156 ± 0.132 μM). At those concentrations, ADA1 would be expected to be functionally dominant due to its higher affinity for adenosine. ADA1 activity in RA SF (mean ± SD 14.4 ± 8.5 IU/liter) was significantly higher than that in OA SF (3.0 ± 1.1 IU/liter) or RA sera (3.0 ± 0.6 IU/liter); moreover, ADA1 activity in RA FLS lysate was the highest among the cell lysates tested. Proinflammatory cytokines did not affect ADA1 activity or ADA mRNA expression in RA FLS.ConclusionElevated ADA1 activity is an intrinsic characteristic of RA FLS, which likely contributes to the pathogenesis of RA by neutralizing the antirheumatic properties of endogenous adenosine.
The role of electronic preprints in chemical communication: Analysis of citation, usage, and acceptance in the journal literature
Authors: Brown Cecelia 
Published: March 2003

AbstractThis study characterizes the usage and acceptance of electronic preprints (e‐prints) in the literature of chemistry. Survey of authors of e‐prints appearing in the Chemistry Preprint Server (CPS) at http://preprints.chemweb.com indicates use of the CPS as a convenient vehicle for dissemination of research findings and for receipt of feedback before submitting to a peer‐reviewed journal. Reception of CPS e‐prints by editors of top chemistry journals is very poor. Only 6% of editors responding allow publication of articles that have previously appeared as e‐prints. Concerns focus on the lack of peer review and the uncertain permanence of e‐print storage. Consequently, it was not surprising to discover that citation analysis yielded no citations to CPS e‐prints in the traditional literature of chemistry. Yet data collected and posted by the CPS indicates that the e‐prints are valued, read, and discussed to a notable extent within the chemistry community. Thirty‐two percent of the most highly rated, viewed, and discussed e‐prints eventually appear in the journal literature, indicating the validity of the work submitted to the CPS. This investigation illustrates the ambivalence with which editors and authors view the CPS, but also gives an early sense of the potential free and rapid information dissemination, coupled with open, uninhibited discussion and evaluation, has to expand, enrich, and vitalize the scholarly discourse of chemical scientists.
A Stochastic Compartmental Model with Long Lasting Infusion
Authors: Ferrante L. , Bompadre S. , Leone L. 
Published: March 2003

AbstractMost of the compartmental models in current use to model pharmacokinetic systems are deterministic. Stochastic formulations of pharmacokinetic compartmental models introduce stochasticity through either a probabilistic transfer mechanism or the randomization of the transfer rate constants. In this paper we consider a linear stochastic differential equation (LSDE) which represents a stochastic version of a one‐compartment linear model when input function undergoes random fluctuations. The solution of the LSDE, its mean value and covariance structure are derived. An explicit likelihood function is obtained either when the process is observed continuously over a period of time or when sampled data are available, as it is generally feasible. We discuss some asymptotic properties of the maximum likelihood estimators for the model parameters. Furthermore we develop expressions for two random variables of interest in pharmacokinetics: the area under the time‐concentration curve, M0(T), and the plateau concentration, xss. Finally the estimation procedure is illustrated by an application to real data.
A Revisit on Comparing the Asymptotic Interval Estimators of Odds Ratio in a Single 2 × 2 Table
Authors: Lui Kung‐Jong , Lin Chii‐Dean 
Published: March 2003

AbstractIt is well known thatCornfield's confidence interval of the odds ratio with the continuity correction can mimic the performance of the exact method. Furthermore, because the calculation procedure of using the former is much simpler than that of using the latter,Cornfield's confidence interval with the continuity correction is highly recommended by many publications. However, all these papers that draw this conclusion are on the basis of examining the coverage probability exclusively. The efficiency of the resulting confidence intervals is completely ignored. This paper calculates and compares the coverage probability and the average length forWoolfs logit interval estimator,Gart's logit interval estimator of adding 0.50,Cornfield's interval estimator with the continuity correction, andCornfield's interval estimator without the continuity correction in a variety of situations. This paper notes thatCornfield's interval estimator with the continuity correction is too conservative, whileCornfield's method without the continuity correction can improve efficiency without sacrificing the accuracy of the coverage probability. This paper further notes that when the sample size is small (say, 20 or 30 per group) and the probability of exposure in the control group is small (say, 0.10) or large (say, 0.90), usingCornfield's method without the continuity correction is likely preferable to all the other estimators considered here. When the sample size is large (say, 100 per group) or when the probability of exposure in the control group is moderate (say, 0.50),Gart's logit interval estimator is probably the best.
Simple and efficient solid support scavenging of excess acyl donors after enzymatic acylations in organic solvents
Authors: Usyatinsky Alexander Ya. , Astakhova Nadezhda M. , Khmelnitsky Yuri L. 
Published: March 2003

AbstractA simple and efficient method for removing excess acyl donors following enzymatic acylations in organic solvents was developed. This method is based on selective chemical scavenging of acyl donors using an amino‐functionalized solid support, and does not affect the desired acylated product. A wide variety of different acyl donors, including vinyl and trifluoroethyl esters and vinyl carbonates, can be quantitatively removed by this method, thus providing a simple and highly efficient tool for purification of reaction products after enzymatic acylation. © 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 82: 379–385, 2003.
Monitoring of a sequencing batch reactor using adaptive multiblock principal component analysis
Authors: Lee Dae Sung , Vanrolleghem Peter A. 
Published: March 2003

AbstractMultiway principal component analysis (MPCA) for the analysis and monitoring of batch processes has recently been proposed. Although MPCA has found wide applications in batch process monitoring, it assumes that future batches behave in the same way as those used for model identification. In this study, a new monitoring algorithm, adaptive multiblock MPCA, is developed. The method overcomes the problem of changing process conditions by updating the covariance structure recursively. A historical set of operational data of a multiphase batch process was divided into local blocks in such a way that the variables from one phase of a batch run could be blocked in the corresponding blocks. This approach has significant benefits because the latent variable structure can change for each phase during the batch operation. The adaptive multiblock model also allows for easier fault detection and isolation by looking at the relationship between blocks and at smaller meaningful block models, and it therefore helps in the diagnosis of the disturbance. The proposed adaptive multiblock monitoring method is successfully applied to a sequencing batch reactor for biological wastewater treatment. © 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 82: 489–497, 2003.
Fusion protein of Vitreoscilla hemoglobin with D‐amino acid oxidase enhances activity and stability of biocatalyst in the bioconversion process of cephalosporin C
Authors: Khang Yong‐Ho , Kim In‐Wook , Hah Young‐Rhan , Hwangbo Jong‐Hyun , Kang Ki‐Kueon 
Published: March 2003

AbstractIn this study we constructed an artificial flavohemoprotein by fusing Vitreoscilla hemoglobin (VHb) with D‐amino acid oxidase (DAO) of Rhodotorula gracilis to determine whether bacterial hemoglobin can be used as an oxygen donor to immobilized flavoenzyme. This chimeric enzyme significantly enhanced DAO activity and stability in the bioconversion process of cephalosporin C. In a 200‐mL bioreactor, the catalytic efficiency of immobilized VHb‐DAO against cephalosporin C was 12.5‐fold higher than that of immobilized DAO, and the operational stability of the immobilized VHb‐DAO was approximately threefold better than that of the immobilized DAO. In the scaled‐up bioprocess with a 5‐L bioreactor, immobilized VHb‐DAO (2500 U/L) resulted in 99% bioconversion of 120 mM cephalosporin C within 60 min at an oxygen flow rate of 0.2 (v/v) × min. Ninety percent of the initial activity of immobilized VHb‐DAO could be maintained at up to 50 cycles of the enzymatic reaction without exogenous addition of H2O2 and flavin adenine dinucleotide (FAD). The purity of the final product, glutaryl‐7‐aminocephalosporanic acid, was confirmed to be 99.77% by high‐performance liquid chromatography (HPLC) analysis. Relative specificity of immobilized VHb‐DAO on D‐α‐aminoadipic acid, a precursor in cephalosporin C biosynthesis, increased twofold, compared with that of immobilized DAO, suggesting that conformational modification of the VHb‐DAO fusion protein may be altered in favor of cephalosporin C. © 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 82: 480–488, 2003.
Role of pericellular matrix in development of a mechanically functional neocartilage
Authors: Graff Ronald D. , Kelley Scott S. , Lee Greta M. 
Published: March 2003

AbstractThe role of the chondrocyte pericellular matrix (PCM) was examined in a three‐dimensional chondrocyte culture system to determine whether retention of the native pericellular matrix could stimulate collagen and proteoglycan accumulation and also promote the formation of a mechanically functional hyaline‐like neocartilage. Porcine chondrocytes and chondrons, consisting of the chondrocyte with its intact pericellular matrix, were maintained in pellet culture for up to 12 weeks. Sulfated glycosaminoclycans and type II collagen were measured biochemically. Immunocytochemistry was used to examine collagen localization as well as cell distribution within the pellets. In addition, the equilibrium compressive moduli of developing pellets were measured to determine whether matrix deposition contributed to the mechanical stiffness of the cartilage constructs. Pellets increased in size and weight over a 6‐week period without apparent cell proliferation. Although chondrocytes quickly rebuilt a PCM rich in type VI collagen, chondron pellets accumulated significantly more proteoglycan and type II collagen than did chondrocyte pellets, indicating a greater positive effect of the native PCM. After 5 weeks in chondron pellets, matrix remodeling was evident by microscopy. Cells that had been uniformly distributed throughout the pellets began to cluster between large areas of interterritorial matrix rich in type II collagen. After 12 weeks, clusters were stacked in columns. A rapid increase in compressive strength was observed between 1 and 3 weeks in culture for both chondron and chondrocyte pellets and, by 6 weeks, both had achieved 25% of the equilibrium compressive stiffness of cartilage explants. Retention of the in vivo PCM during chondrocyte isolation promotes the formation of a mechanically functional neocartilage construct, suitable for modeling the responses of articular cartilage to chemical stimuli or mechanical compres‐ sion. © 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 82: 457–464, 2003.