bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recruitment of intra‐ and extracardiac cells into the myocardial lineage during mouse development
Authors: Kruithof Boudewijn P.T. , van den Hoff Maurice J.B. , Tesink‐Taekema Sabina , Moorman Antoon F.M. 
Published: March 2003

AbstractThe tubular heart differentiates from the bilateral cardiac fields in the splanchnic mesoderm. The expression of smooth muscle proteins has been shown to accompany the early phases of cardiac muscle formation. In this study we show that during elongation of the arterial pole of the mouse linear heart tube, α‐smooth muscle actin (α‐Sma) expression extends in the area that has been shown to become recruited into the myocardial lineage, but does not yet express myocardial markers. These data suggest that α‐Sma identifies mesodermal cells that during subsequent development will be recruited into the myocardial lineage. Myocardium formation is not only observed at the arterial pole, but also at the venous pole and in the intracardiac mesenchyme. This results in the formation of the caval and pulmonary myocardium, the smooth‐walled atrial myocardium, the myocardial atrioventricular septum, and the myocardial outlet septum. To determine whether recruitment into the myocardial lineage also takes place in these regions, the spatiotemporal pattern of expression of α‐Sma and of the myocardial markers sarcoplasmatic reticulum calcium ATPase (Serca2a), α‐myosin heavy chain (Mhc), and β‐Mhc were examined. We show that prior to the expression of myocardial markers, α‐Sma is expressed in these regions, which suggests that these mesodermal cells become recruited into the cardiac lineage after formation of the linear heart tube. Anat Rec Part A 271A:303–314, 2003. © 2003 Wiley‐Liss, Inc.
Hydralazine may induce autoimmunity by inhibiting extracellular signal–regulated kinase pathway signaling
Authors: Deng Chun , Lu Qianjin , Zhang Zhiyong , Rao Tharaknath , Attwood John , Yung Raymond , Richardson Bruce 
Published: March 2003

AbstractObjectiveTo determine whether hydralazine might decrease DNA methyltransferase (DNMT) expression and induce autoimmunity by inhibiting extracellular signal–regulated kinase (ERK) pathway signaling.MethodsThe effect of hydralazine on DNMT was tested in vitro using enzyme inhibition studies, and in vivo by measuring messenger RNA (mRNA) levels and enzyme activity. Effects on ERK, c‐Jun N‐terminal kinase, and p38 pathway signaling were tested using immunoblotting. Murine T cells treated with hydralazine or an ERK pathway inhibitor were injected into mice and anti‐DNA antibodies were measured by enzyme‐linked immunosorbent assay.ResultsIn vitro, hydralazine did not inhibit DNMT activity. Instead, hydralazine inhibited ERK pathway signaling, thereby decreasing DNMT1 and DNMT3a mRNA expression and DNMT enzyme activity similar to mitogen‐activated protein kinase kinase (MEK) inhibitors. Inhibiting T cell ERK pathway signaling with an MEK inhibitor was sufficient to induce anti–double‐stranded DNA antibodies in a murine model of drug‐induced lupus, similar to the effect of hydralazine.ConclusionHydralazine reproduces the lupus ERK pathway signaling abnormality and its effects on DNMT expression, and inhibiting this pathway induces autoimmunity. Hydralazine‐induced lupus could be caused in part by inducing the same ERK pathway signaling defect that occurs in idiopathic lupus.
Serum osteoprotegerin and its ligand in Paget's disease of bone: Relationship to disease activity and effect of treatment with bisphosphonates
Authors: Alvarez L. , Peris P. , Guañabens N. , Vidal S. , Ros I. , Pons F. , Filella X. , Monegal A. , Muñoz‐Gomez J. , Ballesta A. M. 
Published: March 2003

AbstractObjectiveTo test the following hypotheses: 1) osteoprotegerin (OPG) and receptor activator of nuclear factor κB ligand (RANKL) serum levels in patients with Paget's disease are related to disease activity and are different from those in healthy individuals; 2) interleukin‐6 (IL‐6), a cytokine that has been shown to have higher levels in Paget's disease, modulates these factors; and 3) the antiresorptive effect of bisphosphonates in Paget's disease of bone may be mediated through these local factors.MethodsThe study group comprised 31 patients with Paget's disease who received 400 mg/day of oral tiludronate for 3 months. Serum levels of OPG, RANKL, IL‐6, bone alkaline phosphatase (AP), N‐terminal type I procollagen propeptide, urinary N‐terminal crosslinking telopeptide of type I collagen, and urinary α–C‐terminal crosslinking telopeptide of type I collagen were measured at baseline and 1 month after the end of therapy. In addition, the RANKL:OPG ratio was calculated, and disease activity was evaluated at baseline by quantitative bone scintigraphy.ResultsMean baseline OPG values were higher in patients with Paget's disease than in healthy control subjects (P < 0.005), but RANKL and IL‐6 values and RANKL:OPG ratios in the 2 groups were similar. OPG concentrations decreased significantly after treatment with tiludronate (P < 0.005), whereas no significant changes were observed in serum RANKL values. No correlation was found between either bone markers or quantitative scintigraphic indices and serum levels of OPG, RANKL, IL‐6, and RANKL:OPG ratios. Serum OPG decreased significantly only in those patients with baseline OPG values >4.1 pM/liter.ConclusionSerum OPG increases in Paget's disease and decreases after treatment with tiludronate, especially in patients with the highest OPG values. In contrast, RANKL serum levels and RANKL:OPG ratios are unmodified in patients with Paget's disease. Although serum OPG, RANKL, and IL‐6 values were unrelated to disease activity, the increase in OPG may reflect a protective mechanism of the skeleton to compensate for increased bone resorption.
A rare case of juxtaarticular osteoid osteoma of the calcaneus initially misdiagnosed as juvenile chronic arthritis
Authors: Christodoulou Anastasios , Ploumis Avraam , Karkavelas George , Terzidis Ioannis , Tsagias Ioannis 
Published: March 2003

AbstractJuxtaarticular osteoid osteoma is frequently misdiagnosed because the symptoms may mimic arthritis, and radiographs may not be characteristic. A rare case of subtalar pain lasting 5 years in a female teenager is presented here. The initial diagnosis was monarticular juvenile chronic arthritis. Family history was misleading because her mother had rheumatoid arthritis (RA).
Expression of pleiotrophin, an embryonic growth and differentiation factor, in rheumatoid arthritis
Authors: Pufe Thomas , Bartscher Michaela , Petersen Wolf , Tillmann Bernhard , Mentlein Rolf 
Published: March 2003

AbstractObjectivePleiotrophin (PTN), a 15.3‐kd heparin‐binding peptide, is expressed in mesodermal and neuroectodermal cells during development, but rarely in adult tissues. Since developmentally regulated factors often reappear during disease, we sought to determine whether there was PTN expression in the synovial membranes of patients with rheumatoid arthritis (RA).MethodsPTN messenger RNA expression was assayed by quantitative reverse transcriptase–polymerase chain reaction. The protein was localized by immunohistochemistry and quantified by enzyme‐linked immunosorbent assay (ELISA). Effects of PTN on cell proliferation in vitro were determined by DNA measurements.ResultsPTN expression in normal adult synovial membranes and cartilage was barely detectable. However, PTN was strongly up‐regulated in synovial tissues from patients with RA. In contrast, samples from patients with pyogenic arthritis had moderate PTN levels, and those from patients with osteoarthritis had only a slight increase in PTN, as measured by ELISA. In RA patients, PTN was localized primarily in synoviocytes but was also found in endothelial cells of blood vessels. In cultured mouse fibroblasts used as a model, PTN expression was up‐regulated by tumor necrosis factor α and was more weakly up‐regulated by epidermal growth factor. Recombinant PTN stimulated the proliferation of cultured human synoviocytes and the monocyte cell line THP‐1, but not human dermal fibroblasts, in which PTN increased the synthesis of vascular endothelial growth factor.ConclusionIn addition to certain types of cancer, the embryonic growth and differentiation factor PTN is expressed in adults with inflammatory diseases, in particular, RA. Proinflammatory cytokines enhance the expression of PTN. Thus, we propose that PTN is a further paracrine angiogenesis and growth factor for synovial cells in RA.
Inhibition of cartilage degradation: A combined tissue engineering and gene therapy approach
Authors: Kafienah Wael , Al‐Fayez Fayza , Hollander Anthony P. , Barker Michael D. 
Published: March 2003

AbstractObjectiveTo determine if tissue‐engineered cartilage can be protected from cytokine‐induced degradation using a gene therapy approach.MethodsChemical and pantropic retroviral gene transfer methodologies were compared for their ability to introduce a luciferase reporter gene into adult bovine cartilage chondrocytes grown in monolayer. Pantropic retrovirus was then used to transduce these cells with human tissue inhibitor of metalloproteinases 1 (TIMP‐1), and the stability of expression in monolayer or pellet culture was monitored for 6 weeks. Untransduced and TIMP‐1–transduced cells were also used to tissue engineer 3‐dimensional cartilage constructs that were then challenged with interleukin‐1 (IL‐1) for 4 weeks. Conditioned media and residual cartilage were collected for analysis of matrix components, including type II collagen and proteoglycans, and for TIMP‐1 production and matrix metalloproteinase (MMP) activity.ResultsChemical transfection of adult bovine chondrocytes gave rise to short‐lived reporter expression that was virtually undetectable after 4 weeks of culture. In contrast, pantropic retroviral transduction gave rise to stable expression that persisted at a high level for at least 6 weeks. Pantropic transduction of the cells with TIMP‐1 gave rise to similar long‐term expression, both in monolayer and pellet cultures. TIMP‐1–transduced tissue‐engineered cartilage also retained TIMP‐1 expression for an additional 4 weeks of culture in the presence of IL‐1. Compared with control samples, TIMP‐1–transgenic cartilage resisted the catabolic effects of IL‐1, with MMP activity reduced to basal levels and a decreased loss of type II collagen.ConclusionPantropic retroviral transduction permits long‐term expression of potentially therapeutic transgenes in adult tissue‐engineered cartilage. While TIMP‐1 transduction could be used to prevent collagen breakdown, alternative transgenes may be necessary to protect cartilage proteoglycans.
Outcome in adults with juvenile idiopathic arthritis: A quality of life study
Authors: Foster Helen E. , Marshall Nicola , Myers Andrea , Dunkley Pippa , Griffiths Ian D. 
Published: March 2003

AbstractObjectiveTo evaluate quality of life (QOL) in adults with juvenile idiopathic arthritis (JIA), using validated measures of functional disability and generic health status, and to quantify their educational attainment and employment status.MethodsThe adult rheumatology departmental database was used to identify patients. Functional disability and generic health status/QOL were assessed by the Health Assessment Questionnaire (HAQ) and the Short Form 36‐item health profile (SF‐36), respectively. Educational achievement and employment status were assessed by questionnaire.ResultsComplete data were available for 82 of the 101 patients identified. The median age of patients was 30 years, and the median disease duration was 21 years. No deaths were recorded. All subtypes of JIA were represented. Thirty‐nine percent of patients had active disease (based on the physician global assessment scale score). The median HAQ score was 1.125 (range 0–3). SF‐36 scores for bodily pain, general health, physical functioning, vitality, emotion, and social isolation were significantly worse in patients compared with controls, and this trend increased with increasing age of the patients and disease duration. The SF‐36 mental summation scores of patients were low compared with those of controls, for all subtypes of JIA, and this finding was independent of the degree of functional disability (by HAQ and SF‐36 physical summation scores). The educational attainment of patients was comparable to that of local controls, but unemployment rates for patients were 3‐fold higher than those for controls.ConclusionThis is the largest study in which the SF‐36 was used to assess generic health status and QOL in adults with JIA. Many patients had active disease in adulthood, and although the physical outcome of adults with JIA is relatively good, a profound effect on generic health status and QOL was demonstrated for all types of JIA. Furthermore, despite excellent educational attainment, there was a high rate of unemployment among patients.
The rising landscape: A visual exploration of superstring revolutions in physics
Authors: Chen Chaomei , Kuljis Jasna 
Published: March 2003

AbstractKnowledge domain visualization is a visual exploratory approach to the study of the development of a knowledge domain. In this study, we focus on the practical issues concerning modeling and visualizing scientific revolutions. We study the growth patterns of specialties derived from citation and cocitation data on string theory in physics. Special attention is given to the two superstring revolutions since the 1980s. The superstring revolutions are visualized, animated, and analyzed using the general framework of Thomas Kuhn's structure of scientific revolutions. The implications of taking this approach are discussed.
Pathogenic pathways in fluconazole‐induced branchial arch malformations
Authors: Menegola Elena , Broccia Maria L. , Di Renzo Francesca , Giavini Erminio 
Published: March 2003

AbstractBACKGROUNDA widely‐used antimycotic agent, bis‐triazole fluconazole (FLUCO), is able to produce abnormalities to the branchial apparatus (hypoplasia, agenesis, and fusion) in postimplantation rodent embryos cultured in vitro. The branchial apparatus is a complex and transient structure in vertebrate embryos and is essential for the development of the face skeleton. Branchial arch mesenchyme is formed by two different cellular populations: paraxial mesenchyme and ectomesenchyme, which originate from rhombencephalic neural crest cell (NCC) migration. We investigated the possible pathogenic pathways involved in FLUCO‐related branchial arch abnormalities. Perturbations in physiological apoptosis, cell proliferation, NCC migration and branchial mesenchyme induction have been considered.METHODSRat embryos (9.5‐day postcoitum; 1–3 somites) were exposed in vitro to 0 or 500 μM FLUCO. After 24, 36, or 48 hr of culture, embryos were examined for apoptosis (acridine orange method) and cell proliferation (BrdU incorporation and detection method). Rhombencephalic NCC migration was analyzed using immunostaining of NCC (using anti‐CRABP antibodies) and the extracellular matrix (using anti‐fibronectin antibodies). The differentiative capability of the branchial mesenchymes was investigated using anti‐endothelin and anti‐endothelin‐receptor antibodies.RESULTSDuring the whole culture period, no alterations in physiological apoptosis, cell proliferation, and mesenchymal cell induction were observed in FLUCO‐exposed embryos in comparison to controls. On the contrary, severe alterations in NCC migration pathways were observed in FLUCO‐exposed embryos.CONCLUSIONSThe findings suggest that FLUCO produces teratogenic effects by interfering with the cellular and molecular mechanisms that control NCC migration. Birth Defects Research (Part A) 67:116–124, 2003. © 2003 Wiley‐Liss, Inc.
Visualization of alginate–poly‐L‐lysine–alginate microcapsules by confocal laser scanning microscopy
Authors: Strand Berit L. , Mørch Yrr A. , Espevik Terje , Skjåk‐Bræk Gudmund 
Published: March 2003

AbstractConfocal laser scanning microscopy (CLSM) was used to study the distribution of polymers and cross‐linking ions in alginate–poly‐L‐lysine (PLL) –alginate microcapsules made by fluorescent‐labeled polymers. CLSM studies of Ca‐alginate gel beads made in the presence and absence of non‐gelling sodium ions revealed a more inhomogeneous distribution of alginate in beads formed in the absence of non‐gelling ions. In the formation of alginate‐PLL capsules, the polymer gradients in the preformed gel core were destabilized by the presence of non‐gelling ions in the washing step and in the PLL solution. Ca‐alginate gels preserved the inhomogeneous structure by exposure to ion‐free solution in contrast to exposure to non‐gelling ions (Na+). By exchanging Ca2+ with Ba2+ (10 mM), extremely inhomogeneous gel beads were formed that preserved their structure during the washing and exposure to PLL in saline. PLL was shown to bind at the very surface of the alginate core, forming a shell‐like membrane. The thickness of the PLL‐layer increased about 100% after 2 weeks of storage, but no further increase was seen after 2 years of storage. The coating alginate was shown to overlap the PLL layer. No difference in binding could be observed among coating alginates of different composition. This paper shows an easy and novel method to study the distribution of alginate and PLL in intact microcapsules. As the labeling procedures are easy to perform, the method can also be used for a variety of other polymers in other microencapsulation systems. © 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 82: 386–394, 2003.
Electrochemical optical waveguide lightmode spectroscopy (EC‐OWLS): A pilot study using evanescent‐field optical sensing under voltage control to monitor polycationic polymer adsorption onto indium tin oxide (ITO)‐coated waveguide chips
Authors: Bearinger J. P. , Vörös J. , Hubbell J. A. , Textor M. 
Published: March 2003

AbstractA new technique has been developed that combines evanescent‐field optical sensing with electrochemical control of surface adsorption processes. This new technique, termed “electrochemical optical waveguide lightmode spectroscopy” (EC‐OWLS), proved efficient in monitoring molecular surface adsorption and layer thickness changes of an adsorbed polymer layer examined in situ as a function of potential applied to a waveguide in a pilot study. For optical sensing, a layer of indium tin oxide (ITO) served as both a high‐refractive‐index waveguide and a conductive electrode. In addition, an electrochemical flow‐through fluid cell was provided, which incorporated working, reference, and counter electrodes, and was compatible with the constraints of optical sensing. Poly(L‐lysine)‐grafted‐poly(ethylene glycol) (PLL‐g‐PEG) served as a model, polycation adsorbate. Adsorption of PLL‐g‐PEG from aqueous buffer solution increased from 125 to 475 ng/cm2 along a sigmoidal path as a function of increasing potential between 0 and 1.5 V versus the Ag reference electrode. Upon buffer rinse, adsorption was partially reversible when a potential of ≥0.93 V was maintained on the ITO waveguide. However, reducing the applied potential back to 0 V before rinsing resulted in irreversible polymer adsorption. PLL‐g‐PEG modified with biotin demonstrated similar adsorption characteristics, but subsequent streptavidin binding was independent of biotin concentration. Applying positive potentials resulted in increased adsorbed mass, presumably due to polymer chain extension and reorganization in the molecular adlayer. © 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 82: 465–473, 2003.
Calorimetric investigation of anaerobic digestion: Biomass adaptation and temperature effect
Authors: Daverio E. , Spanjers H. , Bassani C. , Ligthart Jos , Nieman H. 
Published: March 2003

AbstractA high‐resolution bench‐scale calorimeter (Bio‐RC1), specially suited for microbiological studies, has been used to investigate the response of an anaerobic granular sludge to repetitive glucose additions at various temperatures. Through the analysis of heat‐evolution profiles resulting from substrate degradation, significant biological events have been identified: the feeble net heat uptake related to aceticlastic methanogenesis has been evaluated, and the detrimental effect of a nutrient deficiency, which led up to 75% decrease in heat production rate, has been detected. After several glucose pulses under non‐limiting nutrient conditions, a reliable and reproducible reference thermal response, which is an important condition for the application of calorimetric measurements to detect inhibitory effects, was finally obtained. Afterward, glucose additions were repeated at various temperatures, and 57% biomass activity reduction, with respect to the reference value at 35°C, was observed when temperature was fixed at 20°C. Additionally, a preliminary toxicity test was also performed by exposing the biomass to increasing formaldehyde concentrations. © 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 82: 499–505, 2003.
Changes in the electrochemical interface as a result of the growth of Pseudomonas fluorescens biofilms on gold
Authors: Busalmen Juan Pablo , de Sánchez Susana R. 
Published: March 2003

AbstractIn this study, variations in corrosion potential and polarization resistance of thin‐film gold electrodes as a result of the growth of Pseudomonas fluorescens biofilms on them are presented. The growth of the volumetric cell fraction of biofilms, as determined by optical sectioning and digital image analysis of phase‐contrast images, was found to be exponential during at least 10 hours of incubation. As a consequence of biofilm growth, an exponential decay of the corrosion potential of gold was observed. Most importantly, an increase in polarization resistance of the interface was observed following a strong linear dependence on the mean thickness of biofilms (r = 0.997), as a consequence of oxygen consumption and diffusion limitations. The results presented indicate that the measurement of polarization resistance may be a suitable technique that could be applied easily in industrial or biotechnological systems for monitoring the formation of biofilms. © 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 82: 619–624, 2003.
NMR Structure of the Single QALGGH Zinc Finger Domain from the Arabidopsis thaliana SUPERMAN Protein
Authors: Isernia Carla , Bucci Enrico , Leone Marilisa , Zaccaro Laura , Di Lello Paola , Digilio Giuseppe , Esposito Sabrina , Saviano Michele , Di Blasio Benedetto , Pedone Carlo , Pedone Paolo V. , Fattorusso Roberto 
Published: March 2003

AbstractZinc finger domains of the classical type represent the most abundant DNA binding domains in eukaryotic transcription factors. Plant proteins contain from one to four zinc finger domains, which are characterized by high conservation of the sequence QALGGH, shown to be critical for DNA‐binding activity. The Arabidopsis thaliana SUPERMAN protein, which contains a single QALGGH zinc finger, is necessary for proper spatial development of reproductive floral tissues and has been shown to specifically bind to DNA. Here, we report the synthesis and UV and NMR spectroscopic structural characterization of a 37 amino acid SUPERMAN region complexed to a Zn2+ ion (Zn–SUP37) and present the first high‐resolution structure of a classical zinc finger domain from a plant protein. The NMR structure of the SUPERMAN zinc finger domain consists of a very well‐defined ββα motif, typical of all other Cys2‐His2 zinc fingers structurally characterized. As a consequence, the highly conserved QALGGH sequence is located at the N terminus of the α helix. This region of the domain of animal zinc finger proteins consists of hypervariable residues that are responsible for recognizing the DNA bases. Therefore, we propose a peculiar DNA recognition code for the QALGGH zinc finger domain that includes all or some of the amino acid residues at positions −1, 2, and 3 (numbered relative to the N terminus of the helix) and possibly others at the C‐terminal end of the recognition helix. This study further confirms that the zinc finger domain, though very simple, is an extremely versatile DNA binding motif.