bluuebunny/crossref_metadata_2025_split huggingface dataset:
T cell aggregation induced through CD43: intracellular signals and inhibition by the immunomodulatory drug leflunomide
Authors: Layseca-Espinosa Esther , Pedraza-Alva Gustavo , Montiel José Luis , del Río Roxana , Fierro Nora A , González-Amaro Roberto , Rosenstein Yvonne 
Published: September 2003

AbstractThe CD43 coreceptor molecule has been shown to participate in lymphocyte adhesion and activation. Leukocyte homotypic aggregation results from a cascade of intracellular signals delivered to the cells upon engagement of different cell-surface molecules with their natural ligands. This phenomenon requires an active metabolism, reorganization of the cytoskeleton, and relocalization of cell-surface molecules. The aim of this study was to identify some of the key members of the signaling cascade leading to T lymphocyte homotypic aggregation following CD43 engagement. CD43-mediated homotypic aggregation of T lymphocytes required the participation of Src kinases, phospholipase C-γ2, protein kinase C, phosphatidylinositol-3 kinase, as well as extracellular-regulated kinase 1/2 and p38. Data shown here suggest that these signaling molecules play a central role in regulating actin cytoskeleton remodeling after CD43 ligation. We also evaluated the ability of immunomodulatory drugs such as leflunomide to block the CD43-mediated homotypic aggregation. Leflunomide blocked the recruitment of targets of the Src family kinases as well as actin polymerization, diminishing the ability of T lymphocytes to aggregate in response to CD43-specific signals, suggesting that this drug might control the migration and recruitment of lymphoid cells to inflamed tissues.
TCR subunit specificity of CTLA-4-mediated signaling
Authors: Siu Eric , Carreno Beatriz M , Madrenas Joaquín 
Published: September 2003

AbstractCytotoxic T-lymphocyte-associated antigen (CTLA)-4 is an activation-induced receptor that down-regulates T cell responses by antagonizing B7-dependent costimulation and/or by transducing a negative signal. The mechanism of CTLA-4-mediated negative signaling is unknown. Recently, it has been postulated that CTLA-4 inhibits T cell activation by causing specific dephosphorylation of the T cell receptor (TCR)-ζ chain of the antigen-receptor complex through an lck-dependent recruitment of the Src homology-2-containing tyrosine phosphatase-2. To test this hypothesis, we generated stably transfected T cell clones expressing doxycycline-inducible CTLA-4 with CD25:TCR-ζ (CD25-ζ) or CD25:CD3-ɛ (CD25-ɛ) fusion proteins. In these clones, ligation of CD25-ζ or of CD25-ɛ with antibodies against CD25 induced full T cell activation, as illustrated by extracellular signal-regulated kinase (ERK) activation and interleukin (IL)-2 production. More importantly, coligation of CTLA-4 with CD25-ζ or of CTLA-4 with CD25-ɛ in the respectively transfected clones inhibited ERK activation and IL-2 production, demonstrating that CTLA-4 does not specifically inhibit signals from TCR-ζ but can also inhibit signals from CD3-ɛ. Our results suggest that the target specificity of CTLA-4 is determined by its coligation with any given transmembrane receptor rather than by its intracellular mediators.
Two Immunoglobulin G Fragment C Receptor Polymorphisms Independently Predict Response to Rituximab in Patients With Follicular Lymphoma
Authors: Weng Wen-Kai , Levy Ronald 
Published: September 2003

Purpose: Although rituximab is now routinely used in the treatment of B-cell non-Hodgkin’s lymphoma, the mechanism of its antitumor effect is not clear. One potential mechanism of action involves antibody-dependent cellular cytotoxicity (ADCC). Two aspects of ADCC influence the effectiveness of this process: the susceptibility of tumor cells and the activation of effector cells via their immunoglobulin G fragment C receptors (FcγRs). Several FcγR polymorphisms have been identified that may affect the killing function of natural killer cells and macrophages.Patients and Methods: The pretreatment tumor cells from 43 patients with follicular lymphoma were tested for their intrinsic susceptibility to rituximab-mediated ADCC. In addition, the FcγRIIIa (CD16) and FcγRIIa (CD32) polymorphisms were determined in an expanded group of 87 patients. The results were then correlated with clinical outcome of these patients.Results: No difference was found between the susceptibility of tumors from patients who clinically responded to rituximab versus those who did not respond. Conversely, both the FcγRIIIa 158 valine/valine and the FcγRIIa 131 histidine/histidine genotypes were found to be independently associated with the response rate and freedom from progression.Conclusion: These data support the hypothesis that ADCC plays an important role in the clinical effect of rituximab at the level of the effector cell. It will be important to include information on Fc receptor polymorphisms in future trials of rituximab therapy.
Probabilistic analysis of braking performance in railways
Authors: Malvezzi M , Presciani P , Allotta B , Toni P 
Published: September 2003

To increase safety and efficiency in the management of railway traffic, a new speed control system, named SCMT, is currently being developed by RFI and Trenitalia for the Italian Railways. Other innovative speed supervision systems are being developed in Europe, such as the ETCS/ERTMS, which will also be installed on the new high-speed line Roma-Napoli.All traffic management systems are generally based on a set of supervision curves relating the allowed velocity of the train to the running distance, in order to ensure the respect of speed restrictions on the line by ‘soft’ or ‘hard’ intervention such as an acoustic and visual warning to the driver (soft) and/or service or emergency braking (hard) in the case of train velocity exceeding the permitted one. To elaborate this set of supervision curves, the on-board unit requires train deceleration depending on time and speed as basic information about the braking behaviour of the train.The implementation of a speed supervision system requires a preliminary definition of braking models that allow the conversion of the general parameters affecting the braking performances of trains (such as a braked weight percentage, goods/passenger brake position, brake equipment, train length, etc.) into a basic deceleration profile as a function of time, during the deceleration rise phase, and of speed, during fully developed braking. The deceleration used to evaluate braking curves is obtained by applying a proper safety margin to the nominal deceleration value (which depends on train characteristics).In this paper a probabilistic analysis of train deceleration is carried out, starting from probability distributions of parameters affecting the braking. For the major parameters, the probability distribution was determined on the basis of technical knowledge and experimental results. The aim of this work is to determine the probability that the real deceleration is lower than the nominal value multiplied by a given safety margin.
Determination of lipophilic descriptors of antihelmintic 6,7‐diaryl‐pteridine derivatives useful for bioactivity predictions
Authors: Reta Mario , Giacomelli Liliana , Santo Marisa , Cattana Rosa , Silber Juana J , Ochoa Carmen , Rodriguez Mercedes , Chana Antonia 
Published: September 2003

AbstractThe liquid chromatographic retention factors extrapolated to pure water, k′w, for several 6,7‐diaryl‐pteridine derivatives in both an octadecylsilane (ODS) and an immobilized artiﬁcial membrane column (IAM.PC.DD2), using acetonitrile–aqueous buffer pH = 7.45 as mobile phase, were obtained. The logarithms of the k′w values in the IAM.PC.DD2 column, log k′wIAM, show good correlation with the calculated values of the octanol–water partition coefﬁcients, log Po/w, showing that the chromatographic parameter can be used as lipophilicity descriptor for the studied pteridines. However, interactions other than the lipophilic ones seem to be involved in the ODS column. Previous studies have shown that pteridines have antihelmintic properties. In spite of the complexity of the studied biological system as compared with the chromatographic one, good correlation between the descriptors obtained in the IAM column and biological activity (expressed as the log of the inhibitory concentration required to obtain up to 50% in the reduction of population growth of nematodes, log IC50) was observed. Copyright © 2003 John Wiley & Sons, Ltd.
Determination of melagatran in rabbit plasma by high‐performance liquid chromatography with automated column switching
Authors: Kim Byoung‐Hyoun , Park Sun Young , Choi Nak Hee , Ok Jong Hoa 
Published: September 2003

AbstractMelagatran is an active thrombin inhibitor showing oral and parenteral bioavailability for antithrombotic therapy. A simple and convenient liquid chromatographic method has been developed and applied to the analysis of melagatran in rabbit plasma. The clean‐up and separation of the sample solutions were performed by automated on‐line column switching HPLC. The method validation shows the suitability of the column switching liquid chromatographic system for the quantitation of melagatran in biological ﬂuids. Copyright © 2003 John Wiley & Sons, Ltd.
The inﬂuence of α1‐acid glycoprotein on collagenase‐3 activity in early rheumatoid arthritis
Authors: Haston J. Louise , FitzGerald Oliver , Kane David , Smith Kevin D. 
Published: September 2003

AbstractThe concentration and glycosylation of α1‐acid glycoprotein (AGP) alter signiﬁcantly during inﬂammation. A deﬁnitive physiological role for AGP remains elusive and is the subject of extensive investigation. This study investigated the inﬂuence of AGP on the activity of collagenase‐3, an important mediator of cartilage destruction in rheumatoid arthritis. AGP was isolated from normal and rheumatoid plasma. Fucosylation was determined by high pH anion‐exchange chromatography; sialylation was assessed following enzymatic digest. Rheumatoid AGP displayed elevated fucosylation and sialylation compared with normal. The inﬂuence of each sample on collagenase‐3 activity was measured ﬂuorometrically. AGP inﬂuenced collagenase‐3 catalysis and collagen binding, with catalytic activity correlating with fucosylation. Rheumatoid AGP exhibited less efﬁcient inhibition than normal plasma AGP. It is hypothesized that AGP within rheumatoid synovial ﬂuid may be inadequate to prevent excessive cartilage destruction and hence may exacerbate the disease process. Copyright © 2003 John Wiley & Sons, Ltd.
Molecular characterization of two host–guest associating hyaluronan derivatives
Authors: Šoltés L. , Mendichi R. 
Published: September 2003

AbstractMolecular characteristics were determined of two high‐molecular‐weight water‐soluble hyaluronan derivatives, namely β‐cyclodextrin (HA‐β‐CD) and N‐acylurea (EDC‐HA). The weight‐average molecular weight (Mw) of HA‐β‐CD and of EDC‐HA, determined with a multi‐angle light scattering detector connected on‐line to a size exclusion chromatographic system, was respectively 185.3 and 86.8 kDa. However the Mw value determined for the equimolar mixture of the two HA derivatives equaled 556.0 kDa. Similarly, the gyration radius of the above equimolar mixture, Rg = 80.6 nm, was signiﬁcantly greater than the values found for the single HA derivative, i.e. 40.2 nm for HA‐β‐CD and 23.8 nm for EDC‐HA. These data indicate that the two kinds of substituents, bound to the polymeric chains, form host–guest/inclusion complexes resulting in polymacromolecular associates/aggregates. Copyright © 2003 John Wiley & Sons, Ltd.
Quantitative determination of DRF‐1042 in human plasma by HPLC: validation and application in clinical pharmacokinetics
Authors: Upreti Vijay V. , Mamidi Rao N.V.S. , Katneni Kasiram , Srinivas Nuggehally R. 
Published: September 2003

AbstractA simple and sensitive high‐performance liquid chromatography (HPLC) method has been developed and validated for the determination of DRF‐1042, a novel orally active camptothecin (CPT) analog, in human plasma. The sample preparation was a simple deproteinization with acidiﬁed methanol yielding almost 100% recovery of DRF‐1042. An isocratic reverse‐phase HPLC separation was developed on a Supelcosil‐LC318 column (250 × 4.6 mm, 5 µm) with mobile phase consisting of 1% v/v triethylamine acetate, pH 5.5 and acetonitrile (80:20, v/v) at a ﬂow rate of 1.0 mL/min. The eluate was monitored with a ﬂuorescence detector set at excitation and emission wavelengths of 370 and 430 nm, respectively. The standard curves were linear (r2 > 0.999) in the concentration ranges 5.0–2004 ng/mL. The lower limit of quantiﬁcation (LLQ) of the assay was 5 ng/mL. The mean measured quality control (QC) concentrations (range 5 ng/mL to 40 µg/mL) deviated from the nominal concentrations in the range of −10.5–0.08 and −14.5–7.97%, inter‐ and intra‐day, respectively. The inter‐ and intra‐day precisions in the measurement of QC samples at four tested concentrations, were in the range 0.64–5.89% relative standard deviation (RSD) and 0.33–14.7% RSD, respectively. The method was found to be suitable for measurement of plasma concentrations above the calibration curve after serial dilutions. Stability of DRF‐1042 was conﬁrmed in a battery of studies, viz., on bench‐top, in the auto‐sampler, in the stock solutions, after four quick freeze–thaw cycles, up to one month at −20C in human plasma and up to 2 months in the ex vivo samples. The method is simple, sensitive and reliable and has been successfully implemented to investigate the clinical pharmacokinetics of DRF‐1042 in cancer patients in a phase I clinical trial. Copyright © 2003 John Wiley & Sons, Ltd.
Reversed‐phase liquid chromatographic method for the analysis of aminoglycoside antibiotics using pre‐column derivatization with phenylisocyanate
Authors: Kim Byoung‐Hyoun , Lee Suk Chin , Lee Hye Jin , Ok Jong Hoa 
Published: September 2003

AbstractA pre‐column derivatization liquid chromatographic method has been developed for the analysis of aminoglycoside antibiotics using phenylisocyanate as a derivatization reagent. Derivatives including kanamycin, neomycin and gentamicin were formed by reaction of the analytes with phenylisocyanate in the presence of triethylamine. Phenylisocyanato groups were attached to corresponding amino groups of aminoglycoside and their molecular mass was conﬁrmed by liquid chromatography–electrospray ionization–mass spectrometry (LC‐ESI‐MS). The experimental conditions for derivatization and separation of aminoglycoside derivatives were optimized and validated. A simple liquid chromatographic method for the determination of aminoglycoside antibiotics was demonstrated. Copyright © 2003 John Wiley & Sons, Ltd.
Improvement of cyclosporin A determination in whole blood by reversed‐phase high‐performance liquid chromatography
Authors: Ouyang Jin , Baeyens Willy R. G. , Duan Jingli , Delanghe Joris 
Published: September 2003

AbstractA chromatographic method was developed for the determination of cyclosporin A in human whole blood using reversed‐phase HPLC at room temperature. Most previous reports carried out this liquid chromatographic separation at temperatures above 70°C. The present procedure greatly improves the detection limit by controlling peak broadening effects, as well as the lifetime of the column at room temperature. Under optimal conditions and using ketoconazole as an internal standard, the calibration graph was linear in the range of 16–1000 µg/L with a relative standard deviation of 3.72% at 150 µg/L and 2.45% at 300 µg/L (n = 11) of cyclosporin A. The detection limit was of 5.0 µg/L cyclosporin A. By this procedure, cyclosporin A pharmacokinetic parameters in healthy Chinese subjects were studied. The developed method could be applied to the quantiﬁcation of cyclosporin A in human blood samples and allows the study of its pharmacokinetics in routine laboratories. Copyright © 2003 John Wiley & Sons, Ltd.
Versican undergoes speciﬁc alterations in the ﬁne molecular structure and organization in human aneurysmal abdominal aortas
Authors: Theocharis A. D. , Tsolakis I. , Hjerpe A. , Karamanos N. K. 
Published: September 2003

AbstractVersican is the major matrix proteoglycan in aortic wall and participates in various biological functions of the tissue. In the present study the molecular characteristics of versican isolated from normal human aorta as well as those of versican expressed in aneurysmal aortic tissue were examined. Versican was isolated by combined anion‐exchange and gel permeation chromatography and was further characterized by high‐performance liquid chromatography, polyacrylamide gel electrophoresis and immunoblotting. In both tissues versican is exclusively substituted with chondroitin sulfate chains, in contrast to other human tissues where both chondroitin and dermatan sulfate chains are attached onto versican core proteins. Except for the signiﬁcant decrease in the concentration of versican in the aneurysmal tissue, this PG undergoes speciﬁc alterations in the aneurysmal tissue. The molecular size of versican isolated from diseased tissue is decreased with a simultaneous increase in the ratio of glycosaminoglycan to protein in this tissue. The latter reﬂect the extensive fragmentation of versican in the diseased tissue and most probably the generation of shorter peptides enriched to glycosaminoglycan chains. Although the size of chondroitin sulfate chains is identical in both versican preparations, a signiﬁcant increase in the percentage of 6‐sulfated disaccharides is observed in chondroitin sulfate chains of versican in aneurysmal aortas, which is accompanied by decrease in 4‐sulfated and non‐sulfated units. Copyright © 2003 John Wiley & Sons, Ltd.
Binding of low molecular mass compounds to proteins studied by liquid chromatographic techniques
Authors: Cserháti Tibor , Forgács Esther , Deyl Zdenek , Miksik Iran , Echardt Adam 
Published: September 2003

AbstractThe newest achievements in the application of miscellaneous liquid chromatographic techniques such as size‐exclusion, ion‐exchange and reversed‐phase high‐performance liquid chromatography, and thin‐layer chromatography for the elucidation of the various aspects of the binding of ligands to proteins are compiled and brieﬂy discussed. Examples of employment in pharmaceutical and clinical chemistry, drug design, enzyme kinetic studies and environmental protection are presented. Copyright © 2003 John Wiley & Sons, Ltd.
Simple method for the determination of rosiglitazone in human plasma using a commercially available internal standard
Authors: Mamidi Rao N. V. S. , Benjamin Biju , Ramesh Mullangi , Srinivas Nuggehally R. 
Published: September 2003

AbstractTo the best of our knowledge, bioanalytical methods to determine rosiglitazone in human plasma reported in literature use internal standards that are not commercially available. Our purpose was to develop a simple method for the determination of rosiglitazone in plasma employing a commercially available internal standard (IS). After the addition of celecoxib (IS), plasma (0.25 mL) samples were extracted into ethyl acetate. The residue after evaporation of the organic layer was dissolved in 750 µL of mobile phase and 50 µL was injected on to HPLC. The separation was achieved using a Hichrom KR 100, 250 × 4.6 mm C18 with a mobile phase composition potassium dihydrogen phosphate buffer (0.01 m, pH 6.5):acetonitrile:methanol (40:50:10, v/v/v). The ﬂow‐rate of the mobile phase was set at 1 mL/min. The column eluate was monitored by ﬂuorescence detector set at an excitation wavelength of 247 nm and emission wavelength of 367 nm. Linear relationships (r2 > 0.99) were observed between the peak area ratio rosiglitazone to IS vs rosiglitazone concentrations across the concentration range 5–1000 ng/mL. The intra‐run precision (%RSD) and accuracy (%Dev) in the measurement of rosiglitazone were <±10.69 and <−12.35%, respectively across the QC levels (50–1000 ng/mL). The extraction efﬁciency was >80% for both rosiglitazone and IS from human plasma. The lower limit of quantitation of the assay was 5 ng/mL. In summary, the methodology for rosiglitazone measurement in plasma was simple, sensitive and employed a commercially available IS. Copyright © 2003 John Wiley & Sons, Ltd.
Cross‐cultural consumer socialization: An exploratory study of socialization influences across three ethnic groups
Authors: Singh Nitish , Kwon Ik‐Whan , Pereira Arun 
Published: September 2003

AbstractAccording to the recent 2000 U.S. Census, the ethnic population in America reached almost 80 million people. However, there is limited research to show how ethnic consumers seek market information and how susceptible they are to different types of personal and media influences. An attempt is made in this study to present a cross‐cultural comparison of ethnic consumer socialization influences. The results of the study indicate that Asian American, Hispanic, and African American young adults significantly differ in their susceptibility to different socialization influences. © 2003 Wiley Periodicals, Inc.
The impact of country of origin on pretrial and posttrial product evaluations: The moderating effect of consumer expertise
Authors: Chiou Jyh‐shen 
Published: September 2003

AbstractThis article examines the effect of country of origin on the pretrial expectation and the posttrial cognitive and affective attitudes when subjects possess different levels of product expertise. Two experiments with 2 (expert vs. novice) × 2 (Japan vs. Taiwan and Italy vs. Taiwan) factorial designs were conducted. One study was conducted on an unambiguous performance product; the other was conducted on an ambiguous performance product. The results showed that country of origin had an impact on the pretrial expectation in both the novice and expert group, regardless of the ambiguity of the product performance. However, the effects on posttrial attitudes were dissimilar between the expert group and the novice group. © 2003 Wiley Periodicals, Inc.
Effects of pallidotomy and levodopa on walking and reaching movements in Parkinson's disease
Authors: Bastian Amy J. , Kelly Valerie E. , Perlmutter Joel S. , Mink Jonathan W. 
Published: September 2003

AbstractWe examined the effects of levodopa and unilateral pallidotomy on quantitative measures of walking and reaching in Parkinson's disease (PD). We also compared quantitative measures of movement with standard clinical rating scales. We used kinematic measures and the Unified Parkinson's Disease Rating Scale (UPDRS) motor subscale (subscale III) to evaluate the movement of 10 people with PD. Subjects were tested after withholding PD medications for at least 8 hours and again 30 to 45 minutes after taking the first morning dose of levodopa. They were studied in this manner before unilateral pallidotomy and then 3.5 to 10 months after surgery. The UPDRS motor subscale was performed in each state. Kinematic data were collected as subjects reached to a target and walked. The UPDRS motor subscale ratings were similar to those reported in the literature: pallidotomy improved the overall motor score and the contralateral bradykinesia + rigidity score, but not the gait + posture score. In contrast, kinematic measures demonstrated that levodopa and pallidotomy had different effects on walking and reaching speed. Both treatments improved walking speed, and the effect was additive. Levodopa improved reaching speed before pallidotomy but did not improve it as much after pallidotomy. Additionally, pallidotomy had inconsistent effects on reaching; some subjects were faster and others were slower. The subjects who initially reached more slowly improved after pallidotomy; the subjects who initially reached more normally (faster) worsened after pallidotomy. On the basis of our results, we speculate that basal ganglia output pathways that control walking and reaching may be distinct, such that bilateral projections to the pedunculopontine area influence walking, whereas ipsilateral thalamocortical projections influence reaching. © 2003 Movement Disorder Society