bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lipopolysaccharide‐induced expression of multiple alternatively spliced MEFV transcripts in human synovial fibroblasts: A prominent splice isoform lacks the C‐terminal domain that is highly mutated in familial mediterranean fever
Authors: Diaz Arturo , Hu Chunbo , Kastner Daniel L. , Schaner Philip , Reginato Anthony M. , Richards Neil , Gumucio Deborah L. 
Published: November 2004

AbstractObjectiveTo investigate the expression of the familial Mediterranean fever (FMF) gene (MEFV) in human synovial fibroblasts.MethodsMEFV messenger RNA in synovial fibroblasts, chondrocytes, and peripheral blood leukocytes (PBLs) was analyzed by semiquantitative and real‐time polymerase chain reaction and ribonuclease protection assay. The subcellular localization of pyrin, the MEFV product, was determined in transfected synovial fibroblasts and HeLa cells with plasmids encoding pyrin isoforms. Native pyrin was detected with an antipyrin antibody.ResultsMEFV was expressed in synovial fibroblasts, but not in chondrocytes. Four alternatively spliced transcripts were identified: an extension of exon 8 (exon 8ext) resulting in a frameshift that predicts a truncated protein lacking exons 9 and 10, the addition of an exon (exon 4a) predicting a truncated protein at exon 5, the in‐frame substitution of exon 2a for exon 2, and the previously described removal of exon 2 (exon 2Δ). Exon 8ext transcripts represented 27% of the total message population in synovial fibroblasts. All other alternatively spliced transcripts were rare. Consensus and alternatively spliced transcripts were induced by lipopolysaccharide in synovial fibroblasts and PBLs. In transfected cells, the proteins encoded by all highly expressed splice forms were cytoplasmic. In contrast, native pyrin was predominantly nuclear in synovial fibroblasts, neutrophils, and dendritic cells, but was cytoplasmic in monocytes.ConclusionSeveral MEFV transcripts are expressed and inducible in synovial fibroblasts. A prominent isoform lacks the C‐terminal domain that contains the majority of mutations found in patients with FMF. While recombinant forms of all major pyrin isoforms are cytoplasmic, native pyrin is nuclear in several cell types. Thus, mechanisms in addition to splicing patterns must control pyrin's subcellular distribution.
Production of endogenous antibiotics in articular cartilage
Authors: Varoga Deike , Pufe Thomas , Harder Jürgen , Meyer‐Hoffert Ulf , Mentlein Rolf , Schröder Jens‐Michael , Petersen Wolf J. , Tillmann Bernhard N. , Proksch Ehrhardt , Goldring Mary B. , Paulsen Friedrich P. 
Published: November 2004

AbstractObjectiveDefensins are broad‐spectrum antimicrobial peptides that are components of innate immunity. To date, only epithelial surfaces and blood cells have been shown to produce these cationic peptides in bactericidal concentrations when challenged with microorganisms or inflammatory cytokines. Infections caused by gram‐negative pathogens occur only infrequently in association with joint surgery. The present study was undertaken to investigate whether this may be explained by intraarticular production of gram‐negative–specialized antimicrobial peptides.MethodsHealthy articular cartilage and cultured T/C‐28a2 chondrocytes were assessed, by reverse transcriptase–polymerase chain reaction (RT‐PCR) and immunohistochemistry, for expression of various antimicrobial peptides. The expression of human β‐defensin 2 (HBD‐2) was studied in cultured chondrocytes after exposure to bacterial supernatants and proinflammatory cytokines and was assayed by real‐time RT‐PCR and immunoblot analysis. A septic arthritis mouse model was used to investigate the regulation of the murine homolog of HBD‐2 in articular cartilage after bacterial inoculation.ResultsHealthy articular cartilage and T/C‐28a2 chondrocytes were able to produce different antimicrobial peptides. After exposure to gram‐negative bacteria and proinflammatory cytokines, expression of cartilage‐derived HBD‐2 strongly increased. Immunoblot analysis revealed up‐regulation of the gram‐negative–specialized HBD‐2 in microbicidal doses. Immunohistochemistry analysis revealed induction of the murine homolog of HBD‐2 in vivo after intraarticular injection of bacteria.ConclusionThis study demonstrated a previously unrecognized function of human chondrocytes. In addition to its biomechanical properties, articular cartilage has the ability to produce antimicrobial substances when challenged with microorganisms. The expression of HBD‐2 in microbicidal doses suggests that antimicrobial peptides may contribute to host defense mechanisms in articular joints.
Histologic analysis of renal leukocyte infiltration in antineutrophil cytoplasmic antibody–associated vasculitis: Importance of monocyte and neutrophil infiltration in tissue damage
Authors: Weidner Sven , Carl Marina , Riess Regine , Rupprecht Harald D. 
Published: November 2004

AbstractObjectiveThe histopathologic lesions in antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV) have been studied extensively, but the exact composition of the cellular infiltrate is unclear. We undertook this study to analyze renal leukocyte infiltration and the cellular distribution within glomeruli and interstitium in 65 renal biopsy samples obtained from patients newly diagnosed as having AAV.MethodsRenal cellular tissue infiltration was assessed with an immunoperoxidase method. Furthermore, the infiltrating cell types were correlated with clinical and histopathologic data.ResultsThe predominant interstitial infiltrating cells were T lymphocytes, while monocytes and, to a lesser extent, granulocytes constituted the dominant infiltrating cell types in glomeruli. Interestingly, lymphocyte infiltration was predominantly periglomerular, especially around glomeruli with sclerosis or heavy crescent formation, while interstitial monocyte and neutrophil infiltration was diffusely distributed over the interstitial tissue. A significant correlation was found for the glomerular infiltration of CD68‐positive macrophages with the presence of glomerular necrosis as well as with the number of glomeruli with crescents (P < 0.0001 and P = 0.005, respectively). No correlation was found for interstitial fibrosis with the infiltration of any leukocyte subset. Furthermore, a significant correlation was found for the interstitial as well as for the glomerular infiltration of CD68‐positive macrophages with serum creatinine concentration at the time of biopsy (P = 0.001 and P = 0.006, respectively).ConclusionThese data underscore a major role of monocytes in addition to neutrophils in the tissue damage of AAV.
Increased susceptibility to rheumatoid arthritis in Koreans heterozygous for HLA–DRB1*0405 and *0901
Authors: Lee Hye‐Soon , Lee Kyung Wha , Song Gwan Gyu , Kim Hyun‐Ah , Kim Shin‐Yoon , Bae Sang‐Cheol 
Published: November 2004

AbstractObjectiveTo investigate the association of susceptibility and protective HLA–DRB1 alleles with rheumatoid arthritis (RA) and its clinical markers in an Asian population.MethodsAll RA patients (n = 574) and control subjects (n = 392) were Korean. HLA–DRB1 typing and further subtyping of all alleles was performed by polymerase chain reaction, sequence‐specific oligonucleotide probe hybridization, and direct DNA sequencing analysis. We used a relative predispositional effects (RPEs) method and a false discovery rate correction method for multiple comparisons.ResultsThe DRB1*0405 and *0901 alleles showed the most significant associations with RA (P = 7.83 × 10−24, odds ratio [OR] 4.40 [95% confidence interval (95% CI) 3.24–5.99], and P = 3.76 × 10−9, OR 2.47 [95% CI 1.82–3.36], respectively). The RPEs test showed that the DRB1*0401 and *0410 alleles conferred susceptibility and that the DRB1*0701, *0802, *1301, *1302, *1403, and *1405 alleles showed significant protective effects. Susceptibility and protective alleles both showed a pattern consistent with additive genetic effects, and each influenced RA independently of the other. The compound heterozygote DRB1*0405/*0901 was associated with the highest risk of RA (corrected P = 1.81 × 10−11, OR 58.2 [95% CI 7.95–425.70]). The mean age at disease onset was ∼4 years earlier or was 3 years earlier, respectively, in patients with at least 1 copy of the DRB1*0405 or the DRB1*0901 allele. Radiographic changes (stages II–IV) were more frequent in patients with at least 1 copy of DRB1*0405 (P = 0.032, 92.6% versus 84.3%, OR 2.33 [95% CI 1.24–4.39]).ConclusionThe DRB1*0405/*0901 heterozygote has the strongest association with RA, suggesting that this heterozygote enhances the susceptibility to RA in Koreans.
Increased prevalence of squamous intraepithelial lesions in systemic lupus erythematosus: Association with human papillomavirus infection
Authors: Tam Lai‐Shan , Chan Alice Y. K. , Chan Paul K. S. , Chang Alexander R. , Li Edmund K. 
Published: November 2004

AbstractObjectiveTo compare the prevalence of abnormal Pap smears in patients with systemic lupus erythematosus (SLE) with that in a large group of healthy controls, and to determine whether SLE itself is an independent risk factor. The association of human papillomavirus (HPV) infection and the use of immunosuppressive agents with abnormal Pap smears in SLE was also assessed.MethodsEighty‐five SLE patients participated in this cross‐sectional study. A sample of cervical cells was collected from each patient for routine cytologic examination. HPV was typed by restriction and sequencing analysis. A structured questionnaire was administered to the subjects to ascertain the possible behavioral and biologic risk factors associated with cervical atypia. Data on 2,080 healthy female subjects were retrieved for comparison.ResultsThe mean (±SD) age of SLE patients and controls was 42 ± 9 years and 44 ± 10 years, respectively. The prevalence of abnormal Pap smears was significantly increased in SLE patients compared with controls (16.5% versus 5.7%). The prevalence of squamous intraepithelial lesions was increased ∼6‐fold in SLE patients (11.8%) compared with controls (2.0%). SLE itself remained an independent risk factor for abnormal Pap smears (odds ratio 3.5, 95% confidence interval 1.8–6.9). The overall prevalence of HPV infection in SLE patients and controls was 11.8% and 7.3%, respectively. However, 10.6% of SLE patients were infected with at least 1 high‐risk type of HPV, compared with 4.2% of controls. Multiple infections were also more common in SLE patients than in controls (4.7% versus 1.1%). There were no significant differences in the use of immunosuppressive agents between SLE patients with normal Pap smears and those with abnormal Pap smears.ConclusionAbnormal Pap smears were more common among SLE patients than controls, even after adjusting for HPV status. SLE‐associated immunosuppression increases susceptibility to high‐risk HPV infection and multiple HPV infections. The use of immunosuppressant agents was not associated with abnormal Pap smears.
Antiarthritic effect of bee venom: Inhibition of inflammation mediator generation by suppression of NF‐κB through interaction with the p50 subunit
Authors: Park Hye Ji , Lee Seong Ho , Son Dong Ju , Oh Ki Wan , Kim Ki Hyun , Song Ho Sueb , Kim Goon Joung , Oh Goo Taeg , Yoon Do Young , Hong Jin Tae 
Published: November 2004

AbstractObjectiveTo investigate the molecular mechanisms of the antiarthritic effects of bee venom (BV) and melittin (a major component of BV) in a murine macrophage cell line (Raw 264.7) and in synoviocytes obtained from patients with rheumatoid arthritis.MethodsWe evaluated the antiarthritic effects of BV in a rat model of carrageenan‐induced acute edema in the paw and in a rat model of chronic adjuvant‐induced arthritis. The inhibitory effects of BV and melittin on inflammatory gene expression were measured by Western blotting, and the generation of prostaglandin E2 (PGE2) and nitric oxide (NO) and the intracellular calcium level were assayed. NF‐κB DNA binding and transcriptional activity were determined by gel mobility shift assay or by luciferase assay. Direct binding of BV and melittin to the p50 subunit of NF‐κB was determined with a surface plasmon resonance analyzer.ResultsBV (0.8 and 1.6 μg/kg) reduced the effects of carrageenan‐ and adjuvant‐induced arthritis. This reducing effect was consistent with the inhibitory effects of BV (0.5, 1, and 5 μg/ml) and melittin (5 and 10 μg/ml) on lipopolysaccharide (LPS; 1 μg/ml)–induced expression of cyclooxygenase 2, cytosolic phospholipase A2, inducible NO synthase, generation of PGE2 and NO, and the intracellular calcium level. BV and melittin prevented LPS‐induced transcriptional and DNA binding activity of NF‐κB via the inhibition of IκB release and p50 translocation. BV (affinity [Kd] = 4.6 × 10−6M) and melittin (Kd = 1.2 × 10−8M) bound directly to p50.ConclusionTarget inactivation of NF‐κB by directly binding to the p50 subunit is an important mechanism of the antiarthritic effects of BV.
Cardiovascular risk factors in women with and without rheumatoid arthritis
Authors: Solomon Daniel H. , Curhan Gary C. , Rimm Eric B. , Cannuscio Carolyn C. , Karlson Elizabeth W. 
Published: November 2004

AbstractObjectiveThe risk of cardiovascular disease (CVD) is increased in patients with rheumatoid arthritis (RA). The objective of this study was to examine the distribution of known CVD risk factors and biomarkers of CVD in women with and without RA.MethodsThis study included two components: an examination of clinical CVD risk factors among women participating in the Nurses' Health Study, a prospective longitudinal cohort, and an analysis of CVD biomarkers among a subgroup of women from this cohort who provided a blood specimen in 1989 (biospecimen cohort). Data regarding clinical risk factors for CVD were collected in 1990 by mailed questionnaire. The diagnosis of RA was confirmed through a structured medical record abstraction. We compared clinical risk factors for CVD and biomarkers of CVD between women with and without RA, adjusting for age, body mass index (BMI), smoking status, and menopause status.ResultsWomen with RA (n = 287) were significantly more likely than women without RA (n = 87,019) to report no alcohol use (48.2% versus 39.4%) and past cigarette smoking (47.8% versus 38.0%). No significant differences between these groups were observed for current smoker status, BMI, regular aspirin use, diabetes, hypertension, physical activity, and family history of early myocardial infarction. In the biospecimen cohort (69 RA cases and 491 controls), the levels of several inflammatory biomarkers linked to CVD were significantly elevated in women with RA, including CRP, fibrinogen, sICAM‐1, sTNFRI, sTNFRII, and osteoprotegerin. Levels of total cholesterol, low‐density lipoprotein, triglycerides, apolipoprotein B, and Lp(a) were similar between groups. Levels of homocysteine were similar, but vitamin B12 was significantly higher among women with RA than among the controls.ConclusionIn women participating in the Nurses' Health Study, most traditional CVD risk factors were similar between those who had RA and those who did not. However, as expected, biomarkers of inflammation associated with CVD were generally elevated in women with RA.
First reported pediatric case of systemic lupus erythematosus associated with prolactinoma
Authors: Reuman Peter D. 
Published: November 2004

AbstractThere is much interest in the possibility that prolactin influences disease activity in systemic lupus erythematosus (SLE). We present the first reported pediatric case of prolactinoma associated with SLE, in a 13‐year‐old white female. The diagnosis of SLE was based on the presence of arthritis, antinuclear antibodies, and double‐stranded DNA, and a chest radiograph showing pleural fluid. The diagnosis of pituitary prolactinoma was based on the histologic features and the presence of amenorrhea, galactorrhea, and an elevated serum prolactin level. Neurosurgical resection and medical therapy with bromocriptine mesylate were independently associated with decreased prolactin levels, loss of arthritis, and reduced levels of inflammatory mediators.
Schadensanalysen an Stahlbeton‐ und Spannbetonbrücken unter Einsatz eines Fuzzy‐Expertensystems
Authors: Lücken Theda 
Published: November 2004

AbstractEs wird eine Vorgehensweise zur Analyse und Bewertung von Schäden an Stahlbeton‐ und Spannbetonbrücken vorgestellt. Sie umfaßt die Teilschritte Auswertung von Untersuchungsergebnissen, Schadensdiagnose, Schadensentwicklungsprognosen und Schadensbewertung. Besonderer Wert wird dabei auf die Berücksichtigung von Unschärfen in sprachlichen Ausdrücken, Entscheidungsvorgängen und unvollständigen Informationen gelegt, die mit Hilfe der Fuzzy‐Logik erfaßt werden. Die abgeleitete Vorgehensweise wird durch ein Fuzzy‐Expertensystem abgebildet. Es dient als Hilfsmittel für praktische Schadensanalysen.
Neue Mischbauweise mit Interner Vorspannung ohne Verbund: Pilotprojekt Mühlenbergbrücke
Authors: Haveresch Karlheinz 
Published: November 2004

AbstractSpannbetonbrücken mit Externer Vorspannung haben eine besonders hohe Qualität. Sie sind deshalb für den Bauherrn sehr attraktiv. Die Anwendbarkeit dieser Bauweise kann aber bei sehr schlanken oder gekrümmten Brückenüberbauten eingeschränkt sein. Der folgende Beitrag stellt eine neue Variante der Mischbauweise vor, die die Einsatzmöglichkeiten der Externen Vorspannung wesentlich erweitern kann. Sie kann darüber hinaus auch erhebliche wirtschaftliche und bauverfahrenstechnische Vorteile gegenüber den bisher gültigen Bauweisen haben. Am Beispiel des Pilotprojektes Mühlenbergbrücke werden statisch‐konstruktive Eigenschaften der neuen Mischbauweise dargestellt.
Rückbau und Neubau der Kepplerbrücke in Rottenburg am Neckar
Authors: Braun Hansjörg , Hofmann Isabell 
Published: November 2004

AbstractDie aus den Nachkriegsjahren stammende alte Kepplerbrücke in Rottenburg am Neckar wies gravierende Schäden auf. Eine Sanierung erwies sich als unwirtschaftlich und bereichsweise wegen Unzugänglichkeit sogar nicht möglich. Aus Überlegungen zu städtebaulichen Aspekten, Hochwasserschutz, Bauzeit, Bauablauf und Unterhaltungsfreundlichkeit entschied sich der Stadtrat für eine bewußt schlanke und elegante Stahlverbundbrücke, die farblich gestaltet werden konnte. Der Neubau besteht aus zwei luftdicht verschweißten, im Werk vorgefertigten, gevouteten Stahlkästen mit obenliegender, schlaff bewehrter Betonfahrbahnplatte.
Efficient water removal in lipase‐catalyzed esterifications using a low‐boiling‐point azeotrope
Authors: Yan Youchun , Bornscheuer Uwe T. , Schmid Rolf D. 
Published: November 2004

AbstractHigh conversions in lipase‐catalyzed syntheses of esters from free acyl donors and an alcohol requires efficient removal of water preferentially at temperatures compatible to enzyme activity. Using a lipase B from Candida antarctica (CAL‐B)‐mediated synthesis of sugar fatty‐acid esters, we show that a mixture of ethyl methylketone (EMK) and hexane (best ratio: 4:1, vo/vo) allows efficient removal of water generated during esterification. Azeotropic distillation of the solvent mixture (composition: 26% EMK, 55% hexane, 19% water) takes place at 59°C, which closely matches the optimum temperature reported for CAL‐B. Water is then removed from the azeotrope by membrane vapor permeation. In case of glucose stearate, 93% yield was achieved after 48 h using an equimolar ratio of glucose and stearic acid. CAL‐B could be reused for seven reaction cycles, with 86% residual activity after 14 d total reaction time at 59°C. A decrease in fatty‐acid chain length as well as increasing temperatures (75°C) resulted in lower conversions. In addition, immobilization of CAL‐B on a magnetic polypropylene carrier (EP 100) facilitated separation of the biocatalyst. © 2002 Wiley Periodicals, Inc. Biotechnol Bioeng 78: 31–34, 2002; DOI 10.1002/bit.10084
Validation of a model for process development and scale‐up of packed‐bed solid‐state bioreactors
Authors: Weber Frans J. , Oostra Jaap , Tramper Johannes , Rinzema Arjen 
Published: November 2004

AbstractWe have validated our previously described model for scale‐up of packed‐bed solid‐state fermenters (Weber et al., 1999) with experiments in an adiabatic 15‐dm3 packed‐bed reactor, using the fungi Coniothyrium minitans and Aspergillus oryzae. Effects of temperature on respiration, growth, and sporulation of the biocontrol fungus C. minitans on hemp impregnated with a liquid medium were determined in independent experiments, and the first two effects were translated into a kinetic model, which was incorporated in the material and energy balances of the packed‐bed model. Predicted temperatures corresponded well with experimental results. As predicted, large amounts of water were lost due to evaporative cooling. With hemp as support no shrinkage was observed, and temperatures could be adequately controlled, both with C. minitans and A. oryzae. In experiments with grains, strong shrinkage of the grains was expected and observed. Nevertheless, cultivation of C. minitans on oats succeeded because this fungus did not form a tight hyphal network between the grains. However, cultivation of A. oryzae failed because shrinkage combined with the strong hyphal network formed by this fungus resulted in channeling, local overheating of the bed, and very inhomogeneous growth of the fungus. For cultivation of C. minitans on oats and for cultivation of A. oryzae on wheat and hemp, no kinetic models were available. Nevertheless, the enthalpy and water balances gave accurate temperature predictions when online measurements of oxygen consumption were used as input. The current model can be improved by incorporation of (1) gas‐solids water and heat transfer kinetics to account for deviations from equilibrium observed with fast‐growing fungi such as A. oryzae, and (2) the dynamic response of the fungus to changes in temperature, which were neglected in the isothermal kinetic experiments. © 2002 John Wiley & Sons, Inc. Biotechnol Bioeng 77: 381–393, 2002; DOI 10.1002/bit.10087
Chemometric evaluation of on‐line high‐pressure liquid chromatography in mammalian cell cultures: Analysis of amino acids and glucose
Authors: Larson Tina M. , Gawlitzek Martin , Evans Heather , Albers Urs , Cacia Jerry 
Published: November 2004

AbstractAn on‐line high‐pressure liquid chromatography (HPLC) system capable of measuring amino acids and carbohydrates was used to study metabolism in mammalian cell culture systems. The HPLC method utilized anion‐exchange chromatography followed by integrated pulsed amperometric detection. The method is capable of measuring 19 amino acids plus glucose with a complete method time of 65 min. In actual cell cultures, the method was shown to be useful for monitoring 17 amino acids plus glucose. The two amino acids that were not accurately monitored were arginine and lysine, possibly due to their elution near the void volume of the column. The HPLC system was used to study variability in metabolism across different cell culture processes, as well as the effect of glucose and glutamine limitation on a single cell culture process. Chemometric analysis was used to draw statistically meaningful conclusions from the highly correlated, multivariate data set that resulted from these experiments. Using chemometrics, variation between processes was linked to differences in uptake rates of seven amino acids. Similarly, lactate concentration, cell density, and aspartate uptake rate were linked to glucose and glutamine limitation. The effect of nutrient limitation on glutamate, alanine, and ammonium was also considered. © 2002 John Wiley & Sons, Inc. Biotechnol Bioeng 77: 553–563, 2002; DOI 10.1002/bit.10116