bluuebunny/crossref_metadata_2025_split huggingface dataset:
A gene–environment interaction between smoking and shared epitope genes in HLA–DR provides a high risk of seropositive rheumatoid arthritis
Authors: Padyukov Leonid , Silva Camilla , Stolt Patrik , Alfredsson Lars , Klareskog Lars 
Published: October 2004

AbstractObjectiveThe main genetic risk factor for rheumatoid arthritis (RA) is the shared epitope (SE) of HLA–DR, while smoking is an important environmental risk factor. We studied a potential gene–environment interaction between SE genes and smoking in the etiology of the 2 major subgroups of RA: rheumatoid factor (RF)–seropositive and RF‐seronegative disease.MethodsA population‐based case–control study involving incident cases of RF‐seropositive and RF‐seronegative RA (858 cases and 1,048 controls) was performed in Sweden. Cases and controls were classified according to their cigarette smoking status and HLA–DRB1 genotypes. The relative risk of developing RA was calculated for different gene/smoking combinations and was compared with the relative risk in never smokers without SE genes.ResultsThe relative risk of RF‐seropositive RA was 2.8 (95% confidence interval [95% CI] 1.6–4.8) in never smokers with SE genes, 2.4 (95% CI 1.3–4.6) in current smokers without SE genes, and 7.5 (95% CI 4.2–13.1) in current smokers with SE genes. Smokers carrying double SE genes displayed a relative risk of RF‐seropositive RA of 15.7 (95% CI 7.2–34.2). The interaction between smoking and SE genes was significant, as measured by the attributable proportion due to interaction, which was 0.4 (95% CI 0.2–0.7) for smoking and any SE, and 0.6 (95% CI 0.4–0.9) for smoking and a double SE. Neither smoking nor SE genes nor the combination of these factors increased the risk of developing RF‐seronegative RA.ConclusionThe disease risk of RF‐seropositive RA associated with one of the classic genetic risk factors for immune‐mediated diseases (the SE of HLA–DR) is strongly influenced by the presence of an environmental factor (smoking) in the population at risk.
Outcomes of hospitalizations for myocardial infarctions and cerebrovascular accidents in patients with systemic lupus erythematosus
Authors: Ward Michael M. 
Published: October 2004

AbstractObjectivePatients with systemic lupus erythematosus (SLE) have increased risks of acute myocardial infarction (AMI) and cerebrovascular accident (CVA), but it is not known whether they have worse outcomes after AMI or CVA compared with patients without SLE. This study compared in‐hospital mortality, length of stay, and other measures of severity (congestive heart failure or need for coronary artery bypass grafting after AMI; discharge to a skilled nursing facility after CVA) between patients with SLE and patients without SLE who were hospitalized for AMI or CVA.MethodsData on all patients hospitalized in California with either AMI or CVA from 1996 to 2000 were abstracted from a state hospitalization database. Outcomes after AMI were compared between 519 patients with SLE and 214,771 patients without SLE, and outcomes after CVA were compared between 905 patients with SLE and 293,326 patients without SLE. Analyses were performed separately for men and women.ResultsAmong women with AMI, there were no differences in the risk of in‐hospital mortality, long length of stay, or congestive heart failure between patients with SLE and those without SLE, but women with SLE were less likely to undergo coronary artery bypass grafting. Outcomes after AMI did not differ between men with SLE and men without SLE. Among women with CVA, there were no differences in outcomes between patients with SLE and patients without SLE. Men with SLE were almost twice as likely to have a long length of stay after CVA than were men without SLE.ConclusionOutcomes after AMI and CVA are generally similar between patients with SLE and those without SLE.
Matrix metalloproteinase 12–dependent cleavage of urokinase receptor in systemic sclerosis microvascular endothelial cells results in impaired angiogenesis
Authors: D'Alessio Silvia , Fibbi Gabriella , Cinelli Marina , Guiducci Serena , Del Rosso Angela , Margheri Francesca , Serratì Simona , Pucci Marco , Kahaleh Bashar , Fan Pansheng , Annunziato Francesco , Cosmi Lorenzo , Liotta Francesco , Matucci‐Cerinic Marco , Del Rosso Mario 
Published: October 2004

AbstractObjectiveDefective angiogenesis, resulting in tissue ischemia, is particularly prominent in the diffuse form of systemic sclerosis (SSc). The present study was undertaken to identify possible differences between normal and SSc microvascular endothelial cells (MVECs) in the expression of the cell‐associated urokinase‐type plasminogen activator (uPA)/uPA receptor (uPAR) system, which is critical in the angiogenic process.MethodsMVECs were isolated from the dermis of healthy individuals and from the dermis of patients with diffuse SSc. The uPA/uPAR system was examined at the protein and messenger RNA levels. Angiogenesis was assayed on Matrigel‐coated porous filters and plates to evaluate cell proliferation, invasion, and capillary morphogenesis. Cleavage of uPAR and the activity of matrix metalloproteinase 12 (MMP‐12) were evaluated by Western blotting.ResultsCompared with MVECs from healthy skin, MVECs from SSc patients showed higher expression of uPAR. However, in SSc MVECs, uPAR undergoes truncation between domain 1 and domain 2, as shown by flow cytometry, enzyme‐linked immunosorbent assay, and Western blotting, a cleavage that is known to impair uPAR functions. These properties of SSc MVECs were associated with poor spontaneous and uPA‐dependent invasion, proliferation, and capillary morphogenesis. The uPAR cleavage occurring in SSc MVECs was associated with overexpression of MMP‐12. SSc MVEC–conditioned medium impaired uPA‐dependent proliferation and invasion as well as capillary morphogenesis in normal MVECs in vitro. Both a general hydroxamate inhibitor of MMP activity and anti–MMP‐12 antibodies restored this SSc MVEC–induced impaired functioning.ConclusionOverproduction of MMP‐12 by SSc MVECs accounts for the cleavage of uPAR and the impairment of angiogenesis in vitro and may contribute to reduced angiogenesis in SSc patients.
A six‐month followup of a randomized trial comparing the efficacy of a lateral‐wedge insole with subtalar strapping and an in‐shoe lateral‐wedge insole in patients with varus deformity osteoarthritis of the knee
Authors: Toda Yoshitaka , Tsukimura Noriko 
Published: October 2004

AbstractObjectiveTo assess the effect of a lateral‐wedge insole with elastic strapping of the subtalar joint on the femorotibial angle in patients with varus deformity of the knee.MethodsThe efficacy of a wedged insole with subtalar straps and that of a traditional wedged insole shoe insert were compared. Sixty‐six female outpatients with knee osteoarthritis (OA) were randomized (according to birth date) to be treated with either the strapped or the traditional inserted insole. Standing radiographs with unilateral insole use were used to analyze the femorotibial angles for each patient. In both groups, the baseline and 6‐month visual analog scale (VAS) scores for subjective knee pain and the Lequesne index scores for knee OA were compared.ResultsThe 61 patients who completed the 6‐month study were evaluated. At baseline, there was no significant difference in the femorotibial angle (P = 0.66) and the VAS score (P = 0.75) between the 2 groups. At the 6‐month assessment, the 29 subjects wearing the subtalar‐strapped insole demonstrated a significantly decreased femorotibial angle (P < 0.0001) and significantly improved VAS scores (P = 0.001) and Lequesne index scores (P = 0.033) compared with their baseline assessments. These significant differences were not observed in the 32 subjects assigned to the traditional shoe‐inserted wedged insole.ConclusionThese results suggest that an insole with a subtalar strap maintained the valgus correction of the femorotibial angle in patients with varus knee OA for 6 months, indicating longer‐term clinical improvement with the strapped insert compared with the traditional insert.
Expression of mitogen‐activated protein kinase phosphatase 1, a negative regulator of the mitogen‐activated protein kinases, in rheumatoid arthritis: Up‐regulation by interleukin‐1β and glucocorticoids
Authors: Toh Myew‐Ling , Yang Yuan , Leech Michelle , Santos Lanie , Morand Eric F. 
Published: October 2004

AbstractObjectiveMitogen‐activated protein kinases (MAPKs) are activated by proinflammatory stimuli. MAPK phosphatases (MKPs), in particular MKP‐1, have been identified as endogenous negative regulators of MAPK activation. Since MAPKs are known to be important in rheumatoid arthritis (RA) synoviocyte activation, this study assessed the expression, regulation, and function of MKP‐1 in RA.MethodsMKP‐1 expression was measured by Western blotting (WB) and real‐time polymerase chain reaction (PCR). RA fibroblast‐like synoviocytes (FLS) were treated with interleukin‐1β (IL‐1β), tumor necrosis factor α, fetal calf serum, and dexamethasone. Expression of MAPKs in RA FLS was analyzed by WB using phosphospecific antibodies, while IL‐6 expression was assessed by real‐time PCR.ResultsMKP‐1 protein and messenger RNA were detected in cultured RA FLS. IL‐1β rapidly up‐regulated MKP‐1, coinciding with reciprocal down‐regulation of ERK, JNK, and p38 MAPK phosphorylation. Dexamethasone rapidly and sustainably up‐regulated MKP‐1, and this also coincided with down‐regulation of ERK, JNK, and p38 MAPK phosphorylation. In addition, dexamethasone augmented IL‐1β–induced up‐regulation of MKP‐1, and this was associated with inhibition of ERK, JNK, and p38 MAPK phosphorylation and IL‐6 expression. Dexamethasone had no effect on the phosphorylation of upstream kinases such as MEKK‐3/6. In the presence of glucocorticoid (GC) receptor antagonist RU 486, the dexamethasone‐mediated up‐regulation of MKP‐1 was impaired. Moreover, inhibition of MKP‐1 expression impaired dexamethasone‐mediated inhibition of MAPK phosphorylation.ConclusionThis study demonstrates the expression of MKP‐1 in RA FLS. Cytokine and GC regulation of MKP‐1 may be important in determining the magnitude of the inflammatory response in RA that is mediated via MAPKs. The effects of GCs in RA may be mediated, in part, via GC receptor–dependent up‐regulation of MKP‐1.
Histone deacetylase inhibitor suppression of autoantibody‐mediated arthritis in mice via regulation of p16INK4a and p21WAF1/Cip1 expression
Authors: Nishida Keiichiro , Komiyama Takamitsu , Miyazawa Shin‐ichi , Shen Zheng‐Nan , Furumatsu Takayuki , Doi Hideyuki , Yoshida Aki , Yamana Jiro , Yamamura Masahiro , Ninomiya Yoshihumi , Inoue Hajime , Asahara Hiroshi 
Published: October 2004

AbstractObjectiveTo examine whether depsipeptide (FK228), a histone deacetylase (HDA) inhibitor, has inhibitory effects on the proliferation of synovial fibroblasts from rheumatoid arthritis (RA) patients, and to examine the effects of systemic administration of FK228 in an animal model of arthritis.MethodsAutoantibody‐mediated arthritis (AMA) was induced in 19 male DBA/1 mice (6–7 weeks old); 10 of them were treated by intravenous administration of FK228 (2.5 mg/kg), and 9 were used as controls. The effects of FK228 were examined by radiographic, histologic, and immunohistochemical analyses and arthritis scores. RA synovial fibroblasts (RASFs) were obtained at the time of joint replacement surgery. In vitro effects of FK228 on cell proliferation were assessed by MTT assay. Cell morphology was examined by light and transmission electron microscopy. The effects on the expression of the cell cycle regulators p16INK4a and p21WAF1/Cip1 were examined by real‐time polymerase chain reaction and Western blot analysis. The acetylation status of the promoter regions of p16INK4a and p21WAF1/Cip1 were determined by chromatin immunoprecipitation assay.ResultsA single intravenous injection of FK228 (2.5 mg/ml) successfully inhibited joint swelling, synovial inflammation, and subsequent bone and cartilage destruction in mice with AMA. FK228 treatment induced histone hyperacetylation in the synovial cells and decreased the levels of tumor necrosis factor α and interleukin‐1β in the synovial tissues of mice with AMA. FK228 inhibited the in vitro proliferation of RASFs in a dose‐dependent manner. Treatment of cells with FK228 induced the expression of p16INK4a and up‐regulated the expression of p21WAF1/Cip1. These effects of FK228 on p16INK4a and p21WAF1/Cip1 were related to the acetylation of the promoter region of the genes.ConclusionOur findings strongly suggest that systemic administration of HDA inhibitors may represent a novel therapeutic target in RA by means of cell cycle arrest in RASFs via induction of p16INK4a expression and increase in p21WAF1/Cip1 expression.
Diphosphines with Expandable Bite Angles: Highly Active Ethylene Dimerisation Catalysts Based on Upper Rim, Distally Diphosphinated Calix[4]arenes
Authors: Lejeune Manuel , Sémeril David , Jeunesse Catherine , Matt Dominique , Peruch Frédéric , Lutz Pierre J. , Ricard Louis 
Published: October 2004

AbstractThe binding properties of two large diphosphines, cone‐5,17‐dibromo‐11,23‐bis(diphenylphosphino)‐25,26,27,28‐tetrapropoxycalix[4]arene (1) and cone‐5,17‐bis(diphenylphosphino)‐25,26,27,28‐tetrapropoxycalix[4]arene (2) toward NiII centres have been investigated. Whatever the starting complex, NiBr2 or [NiCp]BF4, quantitative formation of a chelate complex was observed, illustrating the preorganisation of the ligands. An X‐ray structure determination was carried out for [NiCp⋅1]BF4 which revealed that the nickel atom is positioned to one side of the calixarene axis, the PNiP plane being roughly parallel to the calixarene reference plane. The molecule has C1 symmetry in the solid state, a feature which is also observed in solution at low temperature. As shown by variable‐temperature 1H and 31P NMR studies, the complex undergoes two distinct motions: 1) a fan‐like swinging of the coordination plane which displaces the metal from one side of the calixarene axis to the other, a motion during which the PNiP angle is likely to undergo a significant enlargement; 2) a rapid oscillation of each PPh2 unit about the corresponding NiP bond. In the latter dynamics the two endo‐oriented PPh rings alternately occupy the calixarene entry. The two flexible ligands were assessed in ethylene oligomerisation. Activation with methylaluminoxane of the paramagnetic complexes [NiBr2⋅(1 or 2)] afforded highly active ethylene dimerisation catalysts, with turnover frequencies up to 106 (mol C2H4) (mol Ni)−1 h−1. The selective formation of 1‐butene can be rationally controlled by using low catalyst concentrations.
Sphingosine‐1‐phosphate plays a role in the suppression of lateral pseudopod formation during Dictyostelium discoideum cell migration and chemotaxis
Authors: Kumar Akhilesh , Wessels Deborah , Daniels Karla J. , Alexander Hannah , Alexander Stephen , Soll David R. 
Published: October 2004

AbstractSphingosine‐1‐phosphate (S‐1‐P) is a bioactive lipid that plays a role in diverse biological processes. It functions both as an extracellular ligand through a family of high‐affinity G‐protein‐coupled receptors, and intracellularly as a second messenger. A growing body of evidence has implicated S‐1‐P in controlling cell movement and chemotaxis in cultured mammalian cells. Mutant D. discoideum cells, in which the gene encoding the S‐1‐P lyase had been specifically disrupted by homologous recombination, previously were shown to be defective in pseudopod formation, suggesting that a resulting defect might exist in motility and/or chemotaxis. To test this prediction, we analyzed the behavior of mutant cells in buffer, and in both spatial and temporal gradients of the chemoattractant cAMP, using computer‐assisted 2‐D and 3‐D motion analysis systems. Under all conditions, S‐1‐P lyase null mutants were unable to suppress lateral pseudopod formation like wild‐type control cells. This resulted in a reduction in velocity in buffer and spatial gradients of cAMP. Mutant cells exhibited positive chemotaxis in spatial gradients of cAMP, but did so with lowered efficiency, again because of their inability to suppress lateral pseudopod formation. Mutant cells responded normally to simulated temporal waves of cAMP but mimicked the temporal dynamics of natural chemotactic waves. The effect must be intracellular since no homologs of the S‐1‐P receptors have been identified in the Dictyostelium genome. The defects in the S‐1‐P lyase null mutants were similar to those seen in mutants lacking the genes for myosin IA, myosin IB, and clathrin, indicating that S‐1‐P signaling may play a role in modulating the activity or organization of these cytoskeletal elements in the regulation of lateral pseudopod formation. Cell Motil. Cytoskeleton 59:227–241, 2004. © 2004 Wiley‐Liss, Inc.
Adult glioma incidence trends in the United States, 1977–2000
Authors: Hess Kenneth R. , Broglio Kristine R. , Bondy Melissa L. 
Published: October 2004

AbstractBACKGROUNDSeveral authors have reported an increase in the incidence of brain tumors, especially among the elderly. A more complete understanding of adult glioma incidence trends might provide indications of risk factors for gliomas and contribute to the search for improved therapies.METHODSThe authors used the Surveillance, Epidemiology, and End Results (SEER) registry public use data tapes, which included data on patients with cancer diagnosed between 1973 and 2000. For 3 histologies as well as for 12 histology categories combined, the authors used Poisson regression to model incidence as a function of year of diagnosis, age at diagnosis, race (white or African American), and gender. They used cubic splines to fit age at diagnosis and year of diagnosis and tested for all pair‐wise interactions.RESULTSThe interaction between year of diagnosis and age at diagnosis was significant in all four groups modeled. In glioblastoma, there was also a significant interaction between gender and age at diagnosis. In anaplastic astrocytoma, there was a significant interaction between gender and year of diagnosis. In oligodendroglioma, there was a significant interaction between race and gender. In the 12 histology categories combined, there was a significant interaction between gender and age at diagnosis.CONCLUSIONSThe results in the current study were consistent with other published reports that showed an increase in the incidence of brain tumors using SEER data. Although others have observed increasing incidence trends among the elderly, the authors formally tested and found a statistically significant interaction between age at diagnosis and year of diagnosis. Cancer 2004. © 2004 American Cancer Society.
Fibrinogen receptor antagonists induce conformational changes of the human platelet glycoprotein IIb
Authors: Seyfarth Hans‐Juergen , Koksch Mario 
Published: October 2004

AbstractBackgroundControversial results have been reported concerning the ability of fibrinogen receptor antagonists (fibans) to induce conformational changes in the fibrinogen receptor after binding to it as the initial step of fibrinogen binding and platelet activation.MethodsPlatelets in citrated whole blood were stained with several pairs of anti‐glycoprotein (anti‐GP) IIb–directed monoclonal antibodies conjugated to phycoerythrin (PE) or indirectly labeled with Cy5. Pairs of monoclonal antibodies that induced a high‐fluorescence resonance energy transfer (FRET) efficiency served as tools to detect activation‐dependent changes of GP IIb after addition of adenosine diphosphate and several fibans.ResultsUsing the combination of the clones 5B12‐PE and P2‐biotin/SA‐Cy5, a concentration‐dependent alteration of the GP IIb conformation was observed after addition of tirofiban, eptifibatide, and lotrafiban. Magnitude and kinetics differed among the investigated substances.ConclusionThe newly developed FRET assay allows the direct investigation of conformational changes of GP IIb after addition of platelet agonists or receptor ligands, as shown for three fibans. © 2004 Wiley‐Liss, Inc.
A reconnaissance laser Raman and Fourier transform infrared survey of silcretes from the Kalahari Desert, Botswana
Authors: Nash David J. , Hopkinson Laurence 
Published: October 2004

AbstractThis paper documents the ﬁrst application of laser Raman and Fourier transform infrared vibrational spectroscopic techniques (Raman/FT‐IR) to the analysis of silcrete. Analyses are undertaken at a reconnaissance level on bulk silcrete samples of varying ages, drawn from a range of geomorphological settings across the Kalahari Desert of Botswana. Results suggest that Raman/FT‐IR, combined with inspection of petrographic thin‐sections, provides an effective tool for establishing the range and type of silica polymorphs present within samples. Analyses of Raman and mid‐infrared spectra indicate that the majority of silcretes are dominated by α‐quartz with subordinate moganite. There is, however, considerable inter‐sample variability, ranging from silcretes consisting of almost pure quartz to those containing complex admixtures of disordered microcrystalline or non‐crystalline silica in association with quartz and clays. Taken as a whole, the results are supportive of a similar environment of formation for all samples, with development taking place under broadly semi‐arid conditions. Raman/FT‐IR is also shown to have a number of beneﬁts over other conventional techniques for silcrete analysis, such as X‐ray diffraction. Firstly, inspection of the OH region of the infrared spectrum of bulk samples is shown to have potential for establishing the provenance of quartz clasts within silcrete host sediments, through the identiﬁcation of high‐temperature conditions of crystal growth in detrital quartz grains. Raman and mid‐infrared analyses also permit clay identiﬁcation within silcrete samples where such minerals are not readily resolvable in thin‐section. The technique further allows the relative maturity of silcrete cements to be established, particularly for recently formed silcretes. These are found typically to contain less mature silica polymorphs and incorporate larger quantities of molecular water than α‐quartz dominated silcretes. Comparisons of the range of silica polymorphs identiﬁed using Raman/FT‐IR with those established by petrographic investigation can also reveal evidence of silica paragenesis. This is the case in two stratigraphically older samples from the Kalahari margin in which less stable silica polymorphs appear to have transformed over time to chalcedony and microquartz. Whilst the ‘whole‐rock’ approach used in this survey generates some problems of interpretation, the overall results suggest that the use of micro‐Raman and micro‐FT‐IR techniques should allow even more precise information about the environments of formation and developmental histories of silcrete proﬁles to be produced in the future. Copyright © 2004 John Wiley & Sons, Ltd.