bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reduktiver Elektronentransfer und Transport von Überschusselektronen in DNA
Authors: Wagenknecht Hans‐Achim 
Published: June 2003

AbstractDNA‐vermittelte Ladungstransferprozesse lassen sich prinzipiell in oxidative Lochtransferprozesse und reduktive Elektronentransferprozesse einteilen. Im Hinblick auf die Entstehung von DNA‐Schäden lag das Hauptaugenmerk bisheriger Forschung auf der Untersuchung des oxidativen Lochtransfers oder ‐transportes. Daraus wurden wichtige Informationen beispielsweise über den Mechanismus erhalten. Dagegen hat der Transport oder Transfer von Überschusselektronen ein großes Potenzial für biomedizinische Anwendungen, hauptsächlich in der DNA‐Chiptechnologie. Zur Untersuchung der mechanistischen Details wurden in γ‐Puls‐Radiolyse‐Studien Elektronenacceptoren eingesetzt , die nicht kovalent an DNA gebunden sind. Der entscheidende Nachteil dieses experimentellen Aufbaus liegt darin, dass sowohl die Injektion als auch das Abfangen der Elektronen nicht regiospezifisch erfolgen kann. Kürzlich wurden neue photochemische DNA‐Systeme publiziert, die eine chemische und spektroskopische Untersuchung des reduktiven Elektronentransfers sowie der Wanderung von Überschusselektronen in der DNA erlauben. Basierend auf diesen Resultaten wurde ein Elektronen‐Hopping‐Mechanismus vorgeschlagen, bei dem die Pyrimidin‐Radikalanionen als intermediäre Elektronenträger auftreten.
Hadrian's Wall National Mapping Programme—a World Heritage Site from the air
Authors: Kershaw Antonia 
Published: June 2003

AbstractA survey of Hadrian's Wall is to be undertaken by English Heritage Aerial Survey as part of the National Mapping Programme (NMP). All archaeological features visible on aerial photographs as earthworks or cropmarks will be recorded and mapped. The proposed project area is a broad band along the Roman frontier works and up to 10 km wide, within which sites of all periods will be recorded. This will allow the World Heritage Site to be better understood and managed in its landscape context. Copyright © 2002 John Wiley & Sons, Ltd.
The house of the Bailiff of Sövestad, Sweden—a multi‐method geophysical case study
Authors: Lück E. , Callmer J. , Skånberg T. 
Published: June 2003

AbstractThe village Sövestad, 5 km north of Ystad, in southern Sweden has been known historically since 1085. Over the past 12 years a large number of finds were collected in the furrows of the field south of Sövestad. Some extraordinary finds from medieval time indicate an aristocratic site. To prepare for excavation, geophysical explorations were carried out. The aim was to accurately locate of the main house and to obtain a survey of the archaeological structures in their surroundings. The results of the geophysical investigations are very valuable. The house of the bailiff was found and also many traces of human occupation were observed. The level of modern excavation costs makes this method a valuable alternative to direct excavation as a survey method. However, for the next stage of the study of this manor site a regular excavation will be necessary.The good results obtained so far are an inspiration for further work in the highly interesting region, including a number of manor sites in historical villages close by (e.g. Gundralöv, Katslösa and Stora Herrestad). Only the comparative approach to these aristocratic milieus can contribute substantially to our understanding of this important aspect of rural social life in the Middle Ages. Copyright © 2003 John Wiley & Sons, Ltd.
Frequent infection with a viral pathogen, parvovirus B19, in rheumatic diseases of childhood
Authors: Lehmann Hartwig W. , Knöll Antje , Küster Rolf‐Michael , Modrow Susanne 
Published: June 2003

AbstractObjectiveTo find further evidence of the association of parvovirus B19 infection with juvenile rheumatic diseases, and to get new insights into the immunopathogenesis of these diseases.MethodsPaired serum and synovial fluid samples from 74 children with rheumatic disease were analyzed with respect to their content of viral DNA and antibodies directed against the B19 viral proteins VP1, VP2, and NS1. Control sera from 124 children with noninflammatory bone diseases or growth retardation were also analyzed. The sequence of the viral DNA, amplified by polymerase chain reaction (PCR), was determined. IgG‐complexed virus was isolated from sera and synovial fluid by adsorption to protein A beads. The amount of free virus versus immunocomplexed virus particles was determined by quantification of the viral genomes by quantitative PCR.ResultsTwenty‐six of the 74 patients (35%) had detectable amounts of parvovirus B19 DNA in the serum (n = 22 [30%]) and/or the synovial fluid (n = 16 [22%]), whereas only 9 of the 124 control sera (7%) were positive for the viral DNA (P< 0.0001). Forty‐six patients (62%) had serum IgG against the structural proteins, indicating past infection with B19. NS1‐specific antibodies were detected in sera from 29 patients (39%) and 27 controls (22%) (P< 0.001). In addition, 3 patients (4%) showed VP2‐specific IgM. In 15 patients, viral DNA could be repeatedly detected in followup samples of serum and synovial fluid. Sequencing revealed low‐degree nucleotide variations that are in the range of genotype 1 of parvovirus B19. Immunocomplexed virus was present in varying amounts, both in the sera and in the synovial fluid samples.ConclusionParvovirus B19 is frequently found in serum or synovial fluid of children with rheumatism. The rate of persistent B19 infection in these patients is significantly higher than in age‐matched controls.
A thrombin–cross‐reactive anticardiolipin antibody binds to and inhibits the anticoagulant function of activated protein C
Authors: Hwang Kwan‐Ki , Yang Cheng‐De , Yan Weihong , Grossman Jennifer M. , Hahn Bevra H. , Chen Pojen P. 
Published: June 2003

AbstractObjectiveTo test the hypotheses that some thrombin‐reactive anticardiolipin antibodies (aCL) may bind to protein C (PC) and/or activated PC (APC), and that some of the PC‐ and APC‐reactive aCL may inhibit PC activation and/or the function of APC.MethodsWe studied the reactivity of patient‐derived monoclonal aCL with PC and APC. We examined the effects of the reactive antibodies on PC activation and on the activity of APC in plasma coagulation.ResultsFive of 5 patient‐derived, thrombin‐reactive monoclonal aCL bound to PC and APC. In addition, 1 patient‐derived monoclonal antiprothrombin antibody (APT) that displayed aCL activity and reacted with thrombin also bound to PC and APC. Of these 6 PC‐ and APC‐reactive aCL/APT, all failed to inhibit PC activation, but 1 (CL15) shortened the plasma coagulation time in the presence of exogenous APC and thus inhibited the anticoagulant function of APC.ConclusionMost of the thrombin‐reactive aCL in patients with antiphospholipid syndrome may bind to PC and APC. Of the APC‐reactive aCL, some (like CL15) may inhibit the anticoagulant function of APC and are thus likely to be prothrombotic in the host.
Sex effect on clinical and immunologic quantitative trait loci in a murine model of rheumatoid arthritis
Authors: Adarichev Vyacheslav A. , Nesterovitch Andrew B. , Bárdos Tamás , Biesczat Darci , Chandrasekaran Raman , Vermes Csaba , Mikecz Katalin , Finnegan Alison , Glant Tibor T. 
Published: June 2003

AbstractObjectiveTo explore the effect of sex on clinical and immunologic traits in major histocompatibility complex–matched (H‐2d) F2 hybrid mice with proteoglycan (PG)–induced arthritis and to identify how the quantitative trait locus (QTL) on the X chromosome influences the onset QTL of another chromosome.Methods(BALB/c × DBA/2)F2 hybrid mice were immunized with cartilage PG, and a genome‐wide linkage analysis was performed using >200 simple sequence‐length polymorphic markers. The major clinical traits (susceptibility, onset, and severity) were assessed, and PG‐specific T and B cell responses, and the production of proinflammatory and antiinflammatory cytokines (tumor necrosis factor α, interleukin‐1 [IL‐1], IL‐6, interferon‐γ, IL‐4, IL‐10, and IL‐12) were measured in 133 arthritic and 426 nonarthritic female and male F2 hybrid mice. The major clinical and immunologic traits were linked to genetic loci, and potential linkages among these QTLs and the effect of sex were analyzed.ResultsThirteen QTLs reported in previous studies were confirmed. Binary traits (susceptibility to arthritis) and disease onset were female specific and were identified on chromosomes 3, 7, 10, 11, 13, and X. QTLs for disease severity were mostly male specific and were located on chromosomes 1, 4, 5, 8, 14, 15, and 19. In addition, we identified 4 new QTLs for the onset of arthritis on chromosomes 3, 4, and 11, and 1 new QTL for severity on chromosome 14; all showed a strong gender association. A locus on the X chromosome interacted with a QTL on chromosome 10, and these 2 loci together seemed to control disease incidence and onset. Most of the clinical traits (QTLs) shared common regions with the immunologic traits and frequently showed a locus–locus interaction.ConclusionNumerous immunologic QTLs overlap with clinical QTLs, thus providing information about possible mechanisms underlying QTL function. Disease susceptibility and onset showed predominant linkage with the female sex, under the control of a QTL on the X chromosome, while the severity QTLs were more strongly linked to the male sex.
Mediation of interleukin‐1β–induced transforming growth factor β1 expression by activator protein 4 transcription factor in primary cultures of bovine articular chondrocytes: Possible cooperation with activator protein 1
Authors: Andriamanalijaona R. , Felisaz N. , Kim S.‐J. , King‐Jones K. , Lehmann M. , Pujol J.‐P. , Boumediene K. 
Published: June 2003

AbstractObjectiveInterleukin‐1 (IL‐1) and transforming growth factor β1 (TGFβ1) play major roles in osteoarticular diseases, exerting opposite effects on both the catabolism and anabolism of cartilage matrix. Previous findings suggest that IL‐1 and TGFβ1 could function in a feedback interaction. However, the effect exerted by IL‐1 on expression of TGFβ by articular chondrocytes is, so far, poorly understood. The present study was carried out to determine the influence of IL‐1β on the expression of TGFβ1 by bovine articular chondrocytes (BACs) in primary culture.MethodsBAC primary cultures were treated with IL‐1β, and TGFβ1 messenger RNA (mRNA) steady‐state levels and protein expression were measured by real‐time reverse transcription–polymerase chain reaction and enzyme‐linked immunosorbent assay, respectively. Transient transfection of TGFβ1 gene promoter constructs was performed to delineate the DNA sequences that mediate the IL‐1β effect. Electrophoretic mobility shift assays (EMSAs) and supershift analysis were used to characterize the transcription factors binding to these sequences.ResultsCultured BACs responded to IL‐1β exposure by exhibiting an increase of TGFβ1 expression at both the mRNA and protein levels. The effect was found to be mediated by a major 80‐bp sequence located between −732 and −652 upstream of the transcription initiation site. EMSA and supershift analysis revealed that the transcription factors activator protein 4 (AP‐4) and AP‐1 specifically bound to the −720/−696 part of this sequence under IL‐1β treatment. Overexpression of AP‐4 in the BAC cultures resulted in stimulation of the transcriptional activity of the −732/+11 TGFβ1 promoter construct through the same IL‐1β–responsive element.ConclusionIL‐1β induces an increase of TGFβ1 in articular chondrocytes through activation of AP‐4 and AP‐1 binding to the TGFβ1 gene promoter. These findings may help us understand the role of IL‐1β in the disease process. Notwithstanding its deleterious effect on cartilage, IL‐1 could initiate the repair response displayed by injured cartilage in the early stages of osteoarthritis through its ability to enhance TGFβ1 expression by local chondrocytes.
Epidermal growth factor up‐regulates expression of transforming growth factor β receptor type II in human dermal fibroblasts by phosphoinositide 3‐kinase/Akt signaling pathway: Resistance to epidermal growth factor stimulation in scleroderma fibroblasts
Authors: Yamane Kenichi , Ihn Hironobu , Tamaki Kunihiko 
Published: June 2003

AbstractObjectiveTransforming growth factor β receptors (TGFβRs) are known to be expressed at high levels in several fibrotic diseases, including systemic sclerosis. In the present study, we investigated the mechanism of up‐regulation of TGFβR expression.MethodsThe levels of expression of TGFβR type II (TGFβRII) messenger RNA (mRNA), with or without stimulation by epidermal growth factor (EGF), were evaluated by Northern blot analysis, and the protein levels were determined by immunoblotting. The transcription activity of the TGFβRII gene was examined with luciferase assays using the −1670/+35 TGFβRII promoter luciferase construct.ResultsEGF up‐regulates the expression of TGFβRII mRNA and protein in human dermal fibroblasts. Actinomycin D, an RNA synthesis inhibitor, significantly blocked the EGF‐mediated up‐regulation of TGFβRII mRNA expression, whereas cycloheximide, a protein synthesis inhibitor, did not block this up‐regulation. In addition, EGF treatment did not significantly affect the TGFβRII mRNA half‐life. EGF‐mediated induction of TGFβRII expression was inhibited by treatment of fibroblasts with the selective phosphoinositide 3‐kinase (PI 3‐kinase) inhibitors wortmannin or LY294002, and Akt inhibitor also blocked EGF‐induced expression of TGFβRII. In addition, EGF induced TGFβRII promoter activity, and this induction was significantly blocked by wortmannin, LY294002, or Akt inhibitor. Cotransfection with a dominant‐negative mutant of p85 (the regulatory component of PI 3‐kinase) or Akt significantly reduced the induction of TGFβRII promoter activity by EGF. Moreover, a constitutive active form of p110 (a catalytic component of PI 3‐kinase) induced TGFβRII promoter activity. In addition, scleroderma fibroblasts expressed increased levels of TGFβRII but did not show further up‐regulation of TGFβRII expression by EGF.ConclusionThese results indicate that EGF‐mediated induction of TGFβRII expression occurs at the transcription level, does not require de novo protein synthesis, and involves the PI 3‐kinase/Akt signaling pathway, and that abnormal activation of EGF‐mediated signaling pathways, including PI 3‐kinase or Akt, might play a role in the up‐regulation of TGFβRII in scleroderma fibroblasts.
Influence of stimulatory and suppressive DNA motifs on host susceptibility to inflammatory arthritis
Authors: Zeuner Rainald A. , Verthelyi Daniela , Gursel Mayda , Ishii Ken J. , Klinman Dennis M. 
Published: June 2003

AbstractObjectiveTo examine whether systemic administration of immunostimulatory and immunosuppressive oligodeoxynucleotides (ODNs) alter host susceptibility to inflammatory arthritis.MethodsNormal BALB/c mice were treated systemically with CpG ODNs or suppressive ODNs, and then challenged intraarticularly with CpG DNA. The onset and magnitude of the resulting inflammatory response was monitored.ResultsSystemic delivery of CpG ODNs significantly increased susceptibility to local inflammation, whereas systemic treatment with suppressive ODNs reduced this susceptibility. CD11c+ cells played a key role in mediating host sensitivity to arthritis. These cells were the dominant source of tumor necrosis factor α production in CpG‐stimulated animals and transferred resistance to arthritis from mice treated with suppressive ODNs.ConclusionSystemic exposure to immunostimulatory and immunosuppressive DNA influences host susceptibility to local inflammatory challenge. Current findings raise the possibility that suppressive ODNs may be useful in the prevention/treatment of proinflammatory diseases.
Long‐term anti–tumor necrosis factor antibody therapy in rheumatoid arthritis patients sensitizes the pituitary gland and favors adrenal androgen secretion
Authors: Straub Rainer H. , Pongratz Georg , Schölmerich Jürgen , Kees Frieder , Schaible Thomas F. , Antoni Christian , Kalden Joachim R. , Lorenz Hanns‐Martin 
Published: June 2003

AbstractObjectiveNew insights into the role of tumor necrosis factor (TNF) in the pathogenesis of rheumatoid arthritis (RA) have expanded our understanding about the possible mechanisms by which anti‐TNF antibody therapy reduces local synovial inflammation. Beyond local effects, anti‐TNF treatment may modulate systemic antiinflammatory pathways such as the hypothalamic–pituitary–adrenal (HPA) axis. This longitudinal anti‐TNF therapy study was designed to assess these effects in RA patients.MethodsRA patients were given 5 infusions of anti‐TNF at weeks 0, 2, 6, 10, and 14, with followup observation until week 16. We measured serum levels of interleukin‐6 (IL‐6), adrenocorticotropic hormone (ACTH), 17‐hydroxyprogesterone (17[OH]progesterone), cortisol, cortisone, androstenedione (ASD), dehydroepiandrosterone (DHEA), and DHEA sulfate in 19 RA patients.ResultsUpon treatment with anti‐TNF, we observed a fast decrease in the levels of serum IL‐6, particularly in RA patients who did not receive parallel prednisolone treatment (P = 0.043). In these RA patients who had not received prednisolone, the mean serum ACTH levels sharply increased after every injection of anti‐TNF, which indicates a sensitization of the pituitary gland (not observed for the adrenal gland). During treatment, the ratio of serum cortisol to serum ACTH decreased, which also indicates a sensitization of the pituitary gland (P < 0.001), and which was paralleled by constant cortisol secretion. The adrenal androgen ASD significantly increased relative to its precursor 17(OH)progesterone (P = 0.013) and relative to cortisol (P = 0.009), which indicates a normalization of adrenal androgen production. The comparison of patients previously treated with prednisolone and those without previous prednisolone revealed marked differences in the central and adrenal level of this endocrine axis during long‐term anti‐TNF therapy.ConclusionLong‐term therapy with anti‐TNF sensitizes the pituitary gland and improves adrenal androgen secretion in patients who have not previously received prednisolone treatment. These changes are indicative of normalization of the HPA axis and must therefore be considered as evidence of an additional antiinflammatory influence of anti‐TNF treatment in patients with RA.
Promising outcome of a hip school for patients with hip dysfunction
Authors: Klässbo Maria , Larsson Gerry , Harms‐Ringdahl Karin 
Published: June 2003

AbstractObjectiveTo evaluate, in an exploratory study, a hip school led by physical therapists for patients with hip dysfunction including pain.MethodsPhysicians in primary care and orthopedic units consecutively recruited patients by residential area to a treatment group (T group; n = 77) and a control group (C group; n = 68), mean age 61.8 years, 59 men, 86 women. Ninety‐nine of the 145 subjects had radiologic hip osteoarthritis. Outcome measures were the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and the Nottingham Health Profile (NHP).ResultsAfter hip school (6 months) the T group showed greater reduction on the subscales of pain and activity limitations (WOMAC) than the C group. The subscales sleep disturbances, pain, and physical mobility (NHP) showed improvement for the T group compared with at start. The results for the T group persisted after an additional 6 months.ConclusionA hip school may reduce pain and activity limitations and improve health‐related quality of life for patients with hip dysfunction including pain.
Development of a work instability scale for rheumatoid arthritis
Authors: Gilworth Gill , Chamberlain M. Anne , Harvey Andrew , Woodhouse Amanda , Smith Jacqui , Smyth M. Glyn , Tennant Alan 
Published: June 2003

AbstractObjectivesTo explore the concept of work instability (WI), a state in which the consequences of a mismatch between an individual's functional abilities and the demands of his or her job could threaten continuing employment if not resolved, in people with rheumatoid arthritis (RA). To develop the Work Instability Scale (WIS).MethodsWI in people with RA was explored through qualitative interviews, which were then used to generate items for the WIS.ResultsThrough Rasch analysis and validation against a gold standard of expert vocational assessment, a short 23‐item, self administered, RA WIS was developed.ConclusionThe WIS can be scored in 3 bands indicating low, medium, and high risk of work disability.
The epidemiology of the primary systemic vasculitides in northwest Spain: Implications of the Chapel Hill Consensus Conference definitions
Authors: Gonzalez‐Gay Miguel A. , Garcia‐Porrua Carlos , Guerrero Jose , Rodriguez‐Ledo Pilar , Llorca Javier 
Published: June 2003

AbstractObjectiveTo assess the epidemiology of the primary systemic vasculitides (PSV) in a well‐defined population of southern Europe over a 14‐year period using the Chapel Hill Consensus Conference (CHCC) definitions.MethodsThe case records of all patients 15 years or older with vasculitis diagnosed between January 1988 and December 2001 at a single reference hospital in the Lugo region of northwest Spain were reviewed. Incidence rates were age‐ and sex‐adjusted to the European standard population. Patients were classified as having PSV according to the CHCC definitions.ResultsFifty‐four Lugo residents (29 men) fulfilled the CHCC definitions for PSV. The mean age was 60.7 ± 13.5 years (men: 61.0 ± 13.4; women: 60.4 ± 13.8 years). The overall annual incidence of PSV was 13.07/million (95% confidence interval [95% CI] 8.89–19.22). PSV were slightly more common in men. The age‐specific incidence showed a clear increase with age. A peak in the 55–64 year age group for the whole group of patients with PSV was observed (34.9/million; 95% CI 28.6–42.6). Nonrandom periodical peaks of incidence every 3 years were only observed when the group of PSV was considered as a whole (P = 0.040). The annual incidence was 2.95/million (95% CI 1.44–6.05) for Wegener's granulomatosis (WG) and 7.91/million (95% CI 4.74–13.20) for microscopic polyangiitis (MPA) (P = 0.035). None of the patients with Churg Strauss syndrome (n = 4) lived in a rural area.ConclusionOur observations support an increasing incidence of PSV with age. In patients from northwest Spain defined by the CHCC definitions, MPA is more common than WG.
A comparison of self‐reports of distress and affective disorder diagnoses in rheumatoid arthritis: A receiver operator characteristic analysis
Authors: McQuillan Julia , Fifield Judith , Sheehan T. Joseph , Reisine Susan , Tennen Howard , Hesselbrock Victor , Rothfield Naomi 
Published: June 2003

AbstractObjectiveTo compare 3 commonly used psychiatric symptom checklists (the Center for Epidemiological Studies Depression Scale [CES‐D], the Positive and Negative Affect Schedule, and the Endler Multidimensional Anxiety Scales [EMAS]) to determine their sensitivity, specificity, and ability to discriminate between a disorder (Major Depression [MD], Generalized Anxiety Disorder [GAD]), and no disorder. To compare the checklists for their ability to discriminate between type of disorder (MD and GAD). To evaluate the discriminant ability of the subscales, particularly positive affect; whether the somatic items in the CES‐D artificially inflate affective scores; and the optimal cut off score for the CES‐D.MethodsWe compared the 3 scales to diagnostic criterion of MD, GAD, and comorbid disorder using receiver operator characteristic (ROC) and logistic regression analyses. The sample consisted of a national panel of 415 individuals with rheumatoid arthritis (RA).ResultsEach of the scales had high sensitivity and specificity (areas under the curve: CES‐D = 0.92, negative affect = 0.88, positive affect and EMAS = 0.82). The CES‐D, however, demonstrated better sensitivity and specificity than the positive affect and the EMAS, but not the negative affect scale.ConclusionAll 3 self‐reports have high combined sensitivity and specificity as measures of affective disorders among RA patients.