bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multimethodological approach to study and characterize Forum Novum (Vescovio, central Italy)
Authors: Gaffney V. , Patterson H. , Piro S. , Goodman D. , Nishimura Y. 
Published: November 2004

AbstractThe paper presents the results of an on‐going study of the Roman town and early medieval bishopric of Forum Novum at Vescovio in the middle Tiber valley to the north of Rome. The work forms part of the British School at Rome's Tiber Valley Project, which studies the changing landscapes of the middle Tiber valley as the hinterland of Rome through two millennia, from 1000 BC to AD 1000. At Forum Novum a range of remote sensing techniques are being combined with excavation to examine the extent and organization of a Roman town and its development through time.From 1997 to 2001 a series of topographic and high‐resolution ground‐based remote sensing surveys took place at Forum Novum, which provide a basic map of the ancient centre. The integrated remote sensing surveys were carried out using the magnetic, geoelectric and ground‐penetrating radar (GPR) methods. The analysis of the gradiometric, resistivity and GPR time‐slice maps indicate that many structural foundations and walls of the buildings are still well preserved below the surface.The results, which are presented and discussed in this paper, demonstrate the potential of remote sensing techniques for our understanding of the extent and organization of urban centres. In the case of Forum Novum, where much of the ancient centre lies under modern structures, GPR survey, in particular, proved fundamental. Further, the results of the georadar surveys permitted archaeologists to select key areas of the town for more detailed investigation through excavation. Copyright © 2004 John Wiley & Sons, Ltd.
Measurement of erythrocyte C4d and complement receptor 1 in systemic lupus erythematosus
Authors: Manzi Susan , Navratil Jeannine S. , Ruffing Margie J. , Liu Chau‐Ching , Danchenko Natalya , Nilson Sarah E. , Krishnaswami Shanthi , King Dale E. S. , Kao Amy H. , Ahearn Joseph M. 
Published: November 2004

AbstractObjectiveC4‐derived activation fragments are the only complement ligands present on the surfaces of normal erythrocytes. The significance of this observation is unknown, and the role of erythrocyte‐bound C4 (E‐C4) in human disease has not been explored. More than any other human disease, the pathogenesis of systemic lupus erythematosus (SLE) has been characterized by defects in clearance of complement‐bearing immune complexes via erythrocytes expressing complement receptor 1 (CR1). This study was undertaken to determine whether these functional defects might be reflected by abnormal patterns of E‐C4 and E‐CR1 expression on erythrocytes of patients with SLE.MethodsWe conducted a cross‐sectional study of 100 patients with SLE, 133 patients with other diseases, and 84 healthy controls. Erythrocytes were characterized by indirect immunofluorescence and by flow cytometry for determination of levels of C4d and CR1.ResultsPatients with SLE had higher levels of E‐C4d and lower levels of E‐CR1 than did patients with other diseases (P ≤ 0.001) or healthy controls (P ≤ 0.001). The test was 81% sensitive and 91% specific for SLE versus healthy controls and 72% sensitive and 79% specific for SLE versus other diseases, and it had an overall negative predictive value of 92%.ConclusionThis is the first report of abnormal levels of E‐C4d in human disease. We found that abnormally high levels of E‐C4d and low levels of E‐CR1 are characteristic of SLE, and combined measurement of the 2 molecules has high diagnostic sensitivity and specificity for lupus. Determination of E‐C4d/E‐CR1 levels may be a useful addition to current tests and criteria for SLE diagnosis.
Combination of infliximab and methotrexate therapy for early rheumatoid arthritis: A randomized, controlled trial
Authors: St. Clair E. William , van der Heijde Désirée M. F. M. , Smolen Josef S. , Maini Ravinder N. , Bathon Joan M. , Emery Paul , Keystone Edward , Schiff Michael , Kalden Joachim R. , Wang Ben , DeWoody Kimberly , Weiss Roberta , Baker Daniel ,   Active‐Controlled Study of Patients Receiving Infliximab for the Treatment of Rheumatoid Arthritis of Early Onset Study Group
Published: November 2004

AbstractObjectiveTo compare the benefits of initiating treatment with methotrexate (MTX) and infliximab (anti–tumor necrosis factor α [anti‐TNFα] monoclonal antibody) with those of MTX treatment alone in patients with rheumatoid arthritis (RA) of ≤3 years' duration.MethodsRA patients were eligible if they had active disease and no prior treatment with MTX or a TNFα inhibitor. One thousand forty‐nine patients were randomly assigned in a 4:5:5 ratio to 3 treatment groups: MTX–placebo, MTX–3 mg/kg infliximab, and MTX–6 mg/kg infliximab. MTX dosages were rapidly escalated to 20 mg/week, and infliximab or placebo infusions were given at weeks 0, 2, and 6, and every 8 weeks thereafter through week 46.ResultsAt week 54, the median percentage of American College of Rheumatology improvement (ACR‐N) was higher for the MTX–3 mg/kg infliximab and MTX–6 mg/kg infliximab groups than for the MTX–placebo group (38.9% and 46.7% versus 26.4%, respectively; P < 0.001 for both comparisons). Patients in the MTX–3 mg/kg infliximab and MTX–6 mg/kg infliximab groups also showed less radiographic progression than those receiving MTX alone (mean ± SD changes in van der Heijde modification of the total Sharp score at week 54: 0.4 ± 5.8 and 0.5 ± 5.6 versus 3.7 ± 9.6, respectively; P < 0.001 for each comparison). In addition, physical function improved significantly more in the MTX–3 mg/kg infliximab and MTX–6 mg/kg infliximab groups than in the MTX–placebo group. Infliximab therapy was associated with a significantly higher incidence of serious infections, especially pneumonia.ConclusionFor patients with active RA in its early stages, combination therapy with MTX and infliximab provides greater clinical, radiographic, and functional benefits than treatment with MTX alone.
Enhancement of collagen‐induced arthritis in mice genetically deficient in extracellular superoxide dismutase
Authors: Ross Aron D. , Banda Nirmal K. , Muggli Michele , Arend William P. 
Published: November 2004

AbstractObjectiveTo examine the influence of superoxide on the severity of collagen‐induced arthritis (CIA) in mice.MethodsCIA was induced in DBA/1J mice lacking the extracellular superoxide dismutase (EC‐SOD) gene (knockout [KO]) and in normal DBA/1J mice (wild‐type [WT]).ResultsThe clinical disease activity score was significantly higher in EC‐SOD–KO mice than in WT mice between days 36 and 53, and the histologic scores for joint damage on day 53 increased 2‐fold or more in the EC‐SOD–KO mice. There were no significant differences between the 2 groups of mice in proliferation indices of spleen or lymph node cells in vitro after stimulation with type II collagen. Although both IgG1 and IgG2a anticollagen antibody levels increased in both groups of mice between days 21 and 53, there were no significant differences between the 2 groups. Lipopolysaccharide‐stimulated spleen cells from EC‐SOD–KO mice produced greater levels of tumor necrosis factor α (TNFα) over 48 hours in culture compared with cells from WT mice. Increased steady‐state levels of messenger RNA (mRNA) for interferon‐γ (IFNγ), TNFα, and interleukin‐1β (IL‐1β), and lower levels of IL‐1 receptor antagonist (IL‐1Ra) mRNA were present in the joints of the EC‐SOD–KO mice compared with the WT mice.ConclusionThe absence of EC‐SOD leads to more severe CIA, which may be accompanied by enhanced production of the proinflammatory cytokines IFNγ, TNFα, and IL‐1β, and decreased production of the antiinflammatory cytokine IL‐1Ra in the joints.
Role of NF‐κB transcription factors in antiinflammatory and proinflammatory actions of mechanical signals
Authors: Agarwal Sudha , Deschner James , Long Ping , Verma Anupam , Hofman Cynthia , Evans Christopher H. , Piesco Nicholas 
Published: November 2004

AbstractObjectiveThe mechanisms by which chondrocytes convert biomechanical signals into intracellular biochemical events are not well understood. In this study, we sought to determine the intracellular mechanisms of the magnitude‐dependent actions of mechanical signals.MethodsChondrocytes isolated from rabbit articular cartilage were grown on flexible membranes. Cells were subjected to cyclic tensile strain (CTS) of various magnitudes in the presence or absence of interleukin‐1β (IL‐1β), which was used as a proinflammatory signal for designated time intervals. The regulation of NF‐κB was measured by reverse transcriptase–polymerase chain reaction, electrophoretic mobility shift assay, and immunofluorescence.ResultsCTS of low magnitudes (4–8% equibiaxial strain) was a potent inhibitor of IL‐1β–dependent NF‐κB nuclear translocation. Cytoplasmic retention of NF‐κB and reduction of its synthesis led to sustained suppression of proinflammatory gene induction. In contrast, proinflammatory signals generated by CTS of high magnitudes (15–18% equibiaxial strain) mimicked the actions of IL‐1β and induced rapid nuclear translocation of NF‐κB subunits p65 and p50.ConclusionMagnitude‐dependent signals of mechanical strain utilize the NF‐κB transcription factors as common elements to abrogate or aggravate proinflammatory responses. Furthermore, the intracellular events induced by mechanical overload are similar to those that are initiated by proinflammatory cytokines in arthritis.
Prognostic importance of low body mass index in relation to cardiovascular mortality in rheumatoid arthritis
Authors: Kremers Hilal Maradit , Nicola Paulo J. , Crowson Cynthia S. , Ballman Karla V. , Gabriel Sherine E. 
Published: November 2004

AbstractObjectiveVarious etiologic mechanisms have been implicated in the observed increase in cardiovascular mortality in rheumatoid arthritis (RA). Body mass index (BMI) is associated with cardiovascular mortality in the general population. This study compared the effect of BMI on cardiovascular mortality in a population‐based cohort of subjects with RA with that in a cohort of individuals without RA from the same population.MethodsThe RA cohort comprised all members of an incidence cohort of Rochester, Minnesota residents ages ≥18 years who were first diagnosed with RA (by the American College of Rheumatology 1987 criteria) from 1955 through 1994. An age‐ and sex‐matched comparison cohort of subjects without RA was assembled. Both cohorts were followed up longitudinally through their complete (inpatient, outpatient) medical records beginning at age 18 years and continuing until death, migration, or January 1, 2001, and the details of weight and height changes during this period were recorded. High BMI was defined as a BMI >30 kg/m2 and low BMI as <20 kg/m2. Cox regression models were used to estimate the effect of BMI on cardiovascular mortality after accounting for traditional cardiac risk factors and malignancies.ResultsRA subjects with low BMI at incidence had a significantly higher risk of cardiovascular death (hazard ratio [HR] 3.34, 95% confidence interval [95% CI] 2.23–4.99) compared with non‐RA subjects with normal BMI, after adjusting for age, sex, personal cardiac history, smoking status, and presence of diabetes, hypertension, and malignancies. RA subjects with normal BMI at incidence who experienced low BMI during followup also had a higher risk of cardiovascular death (HR 2.09, 95% CI 1.50–2.92) when compared with non‐RA subjects who maintained normal BMI throughout followup.ConclusionAmong patients with RA, low BMI is associated with a significantly increased risk of cardiovascular death.
Serum cytokine profiles in relapsing polychondritis suggest monocyte/macrophage activation
Authors: Stabler Thomas , Piette Jean‐Charles , Chevalier Xavier , Marini‐Portugal Andre , Kraus Virginia B. 
Published: November 2004

AbstractObjectiveThere is evidence that autoimmunity plays a significant role in the pathogenesis of relapsing polychondritis (RP). This study was designed to investigate circulating levels of various cytokines in relation to the etiology of this rare disorder, and to compare the pattern of cytokine elevations in RP with that in another autoimmune disease, rheumatoid arthritis (RA).MethodsSerum from 22 patients with active RP and an equal number of age‐ and sex‐matched healthy controls and RA patients were available for analysis. The following cytokines were measured: interleukin‐1β (IL‐1β), IL‐2, IL‐4, IL‐5, IL‐6, IL‐7, IL‐8, IL‐10, IL‐12, IL‐13, IL‐17, interferon‐γ (IFNγ), tumor necrosis factor α, granulocyte colony‐stimulating factor (G‐CSF), granulocyte–macrophage colony‐stimulating factor (GM‐CSF), monocyte chemoattractant protein 1 (MCP‐1), and macrophage inflammatory protein 1β (MIP‐1β). Results were analyzed by nonparametric Mann‐Whitney test with Holm stepdown adjustment for multiple testing.ResultsThe levels of 3 of these cytokines showed significant differences between RP patients and controls. Compared with controls, mean serum levels of MCP‐1, MIP‐1β, and IL‐8 were all much higher in patients with active RP. In contrast, RA patients showed a more general increase in all cytokines measured, with much higher levels of IL‐2, IL‐4, IL‐5, IL‐6, IL‐7, IL‐10, IL‐13, IFNγ, G‐CSF, GM‐CSF, MCP‐1, and MIP‐1β compared with controls.ConclusionLevels of 3 serum cytokines were significantly higher in RP patients than in age‐ and sex‐matched controls. One of these 3 cytokines, IL‐8, was not significantly elevated in RA samples. Overall, in RP, a more discrete group of cytokines exhibited significantly increased levels than was found in RA. Each of the 3 cytokines that were elevated in RP is a proinflammatory chemokine, characteristic of activation of the monocyte and macrophage lineage, and in the case of IL‐8, also of neutrophils. These data suggest a major role for a cell‐mediated immune response in the pathophysiology of RP.
The relationship of antiresorptive drug use to structural findings and symptoms of knee osteoarthritis
Authors: Carbone Laura D. , Nevitt Michael C. , Wildy Kathryn , Barrow Karen D. , Harris Fran , Felson David , Peterfy Charles , Visser Marjolein , Harris Tamara B. , Wang Benjamin W. E. , Kritchevsky Stephen B. ,   Health, Aging and Body Composition Study
Published: November 2004

AbstractObjectiveTo examine the cross‐sectional association between use of medications that have a bone antiresorptive effect (estrogen, raloxifene, and alendronate) and both the structural features of knee osteoarthritis (OA), assessed by magnetic resonance imaging (MRI) and radiography, and the symptoms of knee OA in elderly women.MethodsWomen in the Health, Aging and Body Composition Study underwent MRI and radiography of the knee if they reported symptoms of knee OA, and women without significant knee symptoms were selected as controls. MR images of the knee were assessed for multiple features of OA using the Whole‐Organ MRI scoring method, and radiographs were read for Kellgren and Lawrence grade and individual features of OA. Concurrent medication use and knee symptoms were assessed by interview, and knee pain severity was evaluated using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC).ResultsThere were 818 postmenopausal women from whom we obtained MR images of the knee and data on medication use. Among these women, 214 (26.2%) were receiving antiresorptive drugs. We found no significant association between overall use of antiresorptive drugs and the presence of knee pain and radiographic changes of OA of the knee. Use of alendronate, but not estrogen, was associated with less severity of knee pain as assessed by WOMAC scores. Both alendronate use and estrogen use were associated with significantly less subchondral bone attrition and bone marrow edema–like abnormalities in the knee as assessed by MRI, as compared with women who had not received these medications.ConclusionElderly women being treated with alendronate and estrogen had a significantly decreased prevalence of knee OA–related subchondral bone lesions compared with those reporting no use of these medications. Alendronate use was also associated with a reduction in knee pain according to the WOMAC scores.
Inhibition of adjuvant‐induced arthritis by DNA vaccination with the 70‐kd or the 90‐kd human heat‐shock protein: Immune cross‐regulation with the 60‐kd heat‐shock protein
Authors: Quintana Francisco J. , Carmi Pnina , Mor Felix , Cohen Irun R. 
Published: November 2004

AbstractObjectiveAdjuvant arthritis can be induced in Lewis rats by immunization with Mycobacterium tuberculosis (Mt). The mycobacterial 65‐kd heat‐shock protein (Hsp65) is targeted by arthritogenic T cells. However, Hsp65 and the mycobacterial 71‐kd heat‐shock protein are also recognized by T cells that can down‐regulate adjuvant‐induced arthritis (AIA). We have recently demonstrated that vaccination with human Hsp60 DNA inhibits AIA. The present study was undertaken to analyze the role of the T cell responses to self HSP molecules other than Hsp60 in the control of AIA.MethodsLewis rats were immunized with DNA vaccines coding for human Hsp70 or Hsp90 (Hsp70 plasmid [pHsp70] or pHsp90), and AIA was induced. The T cell response to Mt, Hsp60, Hsp70, and Hsp90 (proliferation and cytokine release) was studied, and the T cell response to Hsp60 was mapped with overlapping peptides.ResultsThe Hsp70 or Hsp90 DNA vaccines shifted the arthritogenic T cell response from a Th1 to a Th2/3 phenotype and inhibited AIA. We detected immune crosstalk between Hsp70/90 and Hsp60: both the Hsp70 and Hsp90 DNA vaccines induced Hsp60‐specific T cell responses. Similarly, DNA vaccination with Hsp60 induced Hsp70‐specific T cell immunity. Epitope mapping studies revealed that Hsp60‐specific T cells induced by pHsp70 vaccination reacted with known regulatory Hsp60 epitopes.ConclusionT cell immunity to Hsp70 and to Hsp90, like Hsp60‐specific immunity, can modulate the arthritogenic response in AIA. In addition, our results suggest that the regulatory mechanisms induced by Hsp60, Hsp70, and Hsp90 are reinforced by an immune network that connects their reactivities.
Flachdecken mit Vorspannung ohne Verbund nach DIN 1045‐1: Praxisnahe Hinweise zu Entwurf und Bemessung
Authors: Morgen Karl , Nölting Diedrich , Wollrab Ekkehard 
Published: November 2004

AbstractZum Jahresende 2004 läuft die Übergangsfrist für die seit September 2002 eingeführte Bemessungsnorm DIN 1045 für Tragwerke aus Beton, Stahlbeton und Spannbeton aus. Ein wesentlicher Aspekt des neuen Regelwerks ist die Aufhebung der normativen Trennung für die Bemessung von Stahlbeton‐ und Spannbetonbauteilen. Im Hinblick darauf und unter Berücksichtigung der nationalen Entwicklungen auf dem Gebiet des Spannbetonbaus erscheint es absehbar, daß auch in Deutschland im Hochbau vermehrt vorgespannte Bauteile ausgeführt werden. Von besonderem Interesse für Bauherren, Architekten und entwerfende Ingenieure ist dabei die Perspektive, intern verbundlos verlegte Spannglieder zur Realisierung unterzugsfreier, weitgespannter Deckentragwerke zu verwenden. Insbesondere für schlanke Decken mit großen Spannweiten und erhöhten Anforderungen an die Begrenzung der vertikalen Bauteilverformungen bietet diese Bauart wesentliche Vorteile gegenüber Stahlbetondecken. Der vorliegende Beitrag soll die Entwicklung in diesem Bereich unterstützen, indem aufbauend auf dem heutigen Kenntnisstand praxisorientierte Hinweise zum Entwurf und zur Bemessung von Flachdecken mit Vorspannung ohne Verbund nach DIN 1045‐1 gegeben werden.
Development of an ultrahigh‐temperature process for the enzymatic hydrolysis of lactose. III. Utilization of two thermostable β‐glycosidases in a continuous ultrafiltration membrane reactor and galacto‐oligosaccharide formation under steady‐state conditions
Authors: Petzelbauer Inge , Splechtna Barbara , Nidetzky Bernd 
Published: November 2004

AbstractHydrolysis of lactose by hyperthermophilic β‐glycosidases from the archaea Sulfolobus solfataricus (SsβGly) and Pyrococcus furiosus (CelB) was carried out at 70°C in a continuous stirred‐tank reactor (CSTR) coupled to a 10‐kDa cross‐flow ultrafiltration module to recycle the enzyme. Recirculation rates of ≥1 min−1, reaction of proteins with reducing sugars, and enzyme adsorption onto the membrane are major “operational” factors of enzyme inactivation in the CSTR. They cause the half‐life times of SsβGly and CelB to be reduced two‐ and eight‐fold, respectively, the average value for both enzymes now being ∼5 to 7 days. Using lactose at initial concentrations of 45 and 170 g/L, the CSTR was operated at a constant conversion level of ∼80% for more than 2 weeks without the occurrence of microbial contamination. The productivities for the SsβGly‐catalyzed conversion of lactose were determined at different dilution rates and initial substrate concentrations, and exceed by a factor of ≤2 those observed with CelB under otherwise identical conditions. This difference reflects the approximately eight‐fold stronger product inhibition of CelB by D‐glucose. While the maximum total galacto‐oligosaccharide production (90–100 mM) at 170 g/L lactose in the CSTR was not different from that in the batch reactor (CelB) or was greater by ∼25% (SsβGly), continuous and batchwise reactions with both enzymes differed markedly with regard to relative proportions of the individual saccharide components present at 80% substrate conversion. The CSTR yielded an up to four‐fold greater ratio of disaccharides to trisaccharides concomitant with a 5‐ to 30‐fold larger relative proportion of β‐D‐Galp‐(1→3)‐D‐Glc in the product mixture. The results show that apart from continuous hydrolysis of lactose at 70°C, a CSTR charged with SsβGly or CelB and operated at steady‐state conditions could be a useful reaction system for the production of galacto‐oligosaccharides in which composition is narrower and more easily programmable, in terms of the individual components contained, as compared to the batchwise reaction. © 2002 John Wiley & Sons, Inc. Biotechnol Bioeng 77: 394–404, 2002; DOI 10.1002/bit.10106
Kinetic studies on elemental sulfur oxidation by Acidithiobacillus ferrooxidans: Sulfur limitation and activity of free and adsorbed bacteria
Authors: Ceskova Pavla , Mandl Martin , Helanova Sarka , Kasparovska Jitka 
Published: November 2004

AbstractThe kinetics of sulfur oxidation by Acidithiobacillus ferrooxidans in shaking flasks and a 10‐L reactor was studied. The observed linearity of growth and sulfur oxidation was explained by sulfur limitation. Total cell yield was not significantly different for exponential growth as compared to growth during the sulfur‐limiting phase. Kinetic studies of sulfur oxidation by growing and nongrowing bacteria indicated that both free and adsorbed bacteria oxidize sulfur. Changes in the number of free bacteria rather than cells adsorbed on sulfur were better predictors of the kinetics of sulfur oxidation, indicating that the free bacteria were performing sulfur oxidation. The active growth phase always followed adsorption of bacteria on sulfur; however, the special metabolic role of adsorbed bacteria was unclear. Their activity in sulfur solubilization was considered. © 2002 Wiley Periodicals, Inc. Biotechnol Bioeng 78: 24–30, 2002; DOI 10.1002/bit.10172