bluuebunny/crossref_metadata_2025_split huggingface dataset:
Surface Tension, Phase Separation, and Solidification of Undercooled Cobalt–Copper Alloys
Authors: Egry I. , Herlach D. , Kolbe M. , Ratke L. , Reutzel S. , Perrin C. , Chatain D. 
Published: December 2003

AbstractBy using electromagnetic levitation, liquid Cu–Co alloys can be undercooled below their liquidus temperature into the metastable miscibility gap, leading to a phase separation into a cobalt‐rich L1 phase and a cobalt‐poor L2 phase. This paper reports on experimental and theoretical investigations into the properties of this system, including equilibrium shape, surface, and interfacial tension, phase separation, as well as solidification behavior. Solidification experiments were performed in microgravity in order to minimize the effect of convection on the resulting microstructure.
New antithrombotic 1‐Phthalazinamines with Serotonin Antagonistic Properties
Authors: Johnsen Matthias , Rehse Klaus , Pertz Heinz , Stasch Johannes Peter , Bischoff Erwin 
Published: December 2003

AbstractWe report nineteen 4‐aryl‐ and 4‐arylalkyl‐1‐phthalazinamines (5—8) which we prepared and tested for antithrombotic properties. All compounds were assayed for their antiplatelet activity in the “Born test” with collagen as inducer of the aggregation. N‐[4‐(1H‐1, 2, 4‐triazol‐1‐yl)butyl]‐4‐phenyl‐1‐phthalazin‐amine (7 c) was the most potent compound, having an IC50 of 8 μM. When 5‐HT (Serotonin) was used to start aggregation the N‐(furan‐2‐yl‐methyl)‐4‐phenyl‐1‐pthtalazinamine (8 a) had an IC50 of 2 μM. In vivo potencies were highly significant. N‐[5‐(1H‐1, 2, 4‐triazol‐1‐yl)pentyl]‐4‐phenyl‐1‐phthalazinamine (7 d) inhibited thrombus formation by 12% (P < 0.002) in arterioles and 7% (P < 0.01) in venoles as tested with our laser thrombosis model. For compound 8 a we surprisingly found an antagonism to the 5HT2A receptor, which is most likely the mechanism of the inhibition of aggregation by this compound.
Novel 3, 3a, 4, 5, 6, 7‐Hexahydroindazole and Arylthiazolylpyrazoline derivatives as Anti‐inflammatory Agents
Authors: Nasr Magda N. A. , Said Shehta A. 
Published: December 2003

AbstractA novel series of 7‐benzylidene‐3, 3a, 4, 5, 6, 7‐hexahydro‐3‐phenyl‐2H‐indazole substituted at the 2‐position were synthesized. The reaction of 2, 6‐bis‐benzylidenecyclohexanone (1) with thiosemicarbazide in the presence of NaOH afforded a mixture of the 3‐H, 3a‐H trans 2 and cis 2a diastereoisomers which have been separated by fractional recrystallization. Interaction of the first intermediate 2 with substituted phenacyl bromides, aromatic aldehydes and chloroacetic acid in presence of a mixture of acetic acid and acetic anhydride, and 2, 3‐dichloroquinoxaline yielded the corresponding 7‐benzylidene‐3, 3a, 4, 5, 6, 7‐hexahydro‐3‐phenyl‐2H‐indazole derivatives substituted at the 2‐position with 4‐aryl‐2‐thiazolyl 3a, b, 5‐arylidene‐4, 5‐dihydro‐4‐oxo‐2‐thiazolyl 4a, b and thiazolo[4, 5‐b]quinoxalin‐2‐yl 5, respectively. Moreover, the other intermediates 3, 5‐diaryl‐1‐thiocarbamoyl‐2‐pyrazolines 7a—d were reacted with the previously‐mentioned reagents and gave the corresponding 3, 5‐diaryl‐1‐(4‐aryl‐2‐thiazolyl)‐2‐pyrazolines 8a—h, 3, 5‐diaryl‐1‐(5‐arylidene‐4, 5‐dihydro‐4‐oxo‐2‐thiazolyl)‐2‐pyrazolines 9a—d and 3, 5‐diaryl‐1‐(thiazolo[4, 5‐b]quinoxalin‐2‐yl)‐2‐pyrazoline derivatives 10a, b, respectively. Some of the newly prepared compounds were subjected to evaluation for their anti‐inflammatory activity. The structures of the new compounds were confirmed by elemental analyses as well as 1H‐NMR, IR, and MS data.
Synthesis and In Vitro Antibacterial Evaluation of Novel Imidazo[2′, 1′:5, 1]‐1, 2, 4‐triazolo[4, 3‐c]‐quinazoline Derivatives of 5‐Thioxo‐1, 2, 4‐triazole, 4‐Oxothiazolidine, and their Open‐chain Counterparts
Authors: Nasr Magda N. , Gineinah Magdy M. , El‐Bendary Eman R. 
Published: December 2003

AbstractTwo novel series of imidazo[2′, 1′:5, 1]‐1, 2, 4‐triazolo[4, 3‐c]quinazolines bearing 5‐thioxo‐1, 2, 4‐triazoles, 6a—f, and 4‐oxothiazolidines, 7a—f, were synthesized from corresponding thiosemicarbazide derivatives, 5a—f. The stepwise methodology applied to the preparation of compounds 5a—f was initiated with reaction of the parent 3‐amino‐1, 2, 4‐triazolo[4, 3‐c]quinazolines, 2, with ethyl 2‐chloroacetoacetate resulting in annelation of the imidazole ring to give esters, 3a—c. However, hydrazinolysis of these ester derivatives gave the corresponding acid hydrazides, 4a—c, which on reaction with the appropriate alkyl isothiocyanate yielded compounds 5a—f. In turn, compounds 5, were cyclized with potassium hydroxide or with ethyl bromoacetate to give the corresponding thioxotriazoles 6 and oxothiazolidines 7, respectively. All synthesized compounds were screened for their in vitro antibacterial activity against various Gram‐positive and Gram‐negative bacteria. Some test compounds were found to possess potent antibacterial activities. Compound, 7f, exhibited much higher potency than the reference standard ciprofloxacin, against both types of bacteria, particularly, Gram‐positive organisms.
Preparation of Fluorescent Nonpeptidic Neuropeptide Y Receptor Ligands: Analogues of the Quinazoline‐type Anti‐obesity Y5 Antagonist CGP 71683A
Authors: Li Liantao , Mayer Matthias , Schneider Erich , Schreiber Elvira , Bernhardt Günther , Peng Shiqi , Buschauer Armin 
Published: December 2003

AbstractAs part of a programme to develop fluorescence‐based methods for the study of the interactions between G‐protein coupled receptors (GPCRs) and their ligands the preparation of low molecular weight fluorescence‐labelled neuropeptide Y (NPY) Y5 antagonists is reported. The naphthylsulfonyl group in the potent quinazoline‐type NPY Y5 receptor antagonist CGP 71683A was replaced with a dansyl, nitrobenzoxadiazole (NBD) or acridine‐9‐carbonyl group. In radioligand binding studies on human Y5 receptor expressing HEC‐1B cells the substances labelled with acridine (Ki 311 nM) and NBD (Ki > 1000 nM) proved to be moderately active or inactive, respectively. By contrast, a Ki value of 49 nM was found for the dansyl analogue compared to 2 nM for CGP 71683A. No binding to Y1 receptors (SK‐N‐MC cells, displacement of [3H]propionyl‐NPY) was detected for the new compounds at concentrations ≤ 1 μM.
Suppression of osteoclastogenesis in rheumatoid arthritis by induction of apoptosis in activated CD4+ T cells
Authors: Ogawa Yukie , Ohtsuki Masahiko , Uzuki Miwa , Sawai Takashi , Onozawa Yoshiko , Nakayama Junichi , Yonemura Akiko , Kimura Tomoatsu , Matsuno Hiroaki 
Published: December 2003

AbstractObjectiveTo examine the suppressive effect of anti‐human Fas monoclonal antibody (mAb) on osteoclastogenesis in rheumatoid arthritis (RA) both in vitro and in vivo.MethodsFor in vitro analysis, activated CD4+ T cells derived from peripheral blood mononuclear cells were left untreated or were treated with humanized anti‐human Fas mAb (R‐125224) and cocultured with human monocytes. On day 12, the number of tartrate‐resistant acid phosphatase (TRAP)–positive multinucleated cells was counted. For in vivo analysis, tissue derived from human RA pannus was implanted with a slice of dentin subcutaneously in the backs of SCID mice (SCID‐HuRAg‐pit model). R‐125224 was administered intravenously once a week for 3 weeks. The implanted tissue and dentin slice were removed, and the pits formed on the dentin slice were analyzed.ResultsIn vitro, coculture of activated CD4+ T cells and peripheral monocytes induced osteoclastogenesis. The number of TRAP‐positive multinucleated cells was reduced when activated CD4+ T cells were treated with R‐125224. We established a new animal model for monitoring osteoclastogenesis, SCID‐HuRAg‐pit. We found that with R‐125224 treatment, the number of pits formed on the implanted dentin slices was significantly reduced and the number of lymphocytes in the implanted RA synovial tissue was dramatically reduced in this model.ConclusionThis is the first study to demonstrate the suppressive effect of anti‐human Fas mAb on osteoclastogenesis in RA synovial tissues through the induction of T cell apoptosis. Induction of apoptosis of infiltrated lymphocytes could be a useful therapeutic strategy for RA, in terms of suppressing both inflammation and bone destruction.
G1 domain of aggrecan cointernalizes with hyaluronan via a CD44‐mediated mechanism in bovine articular chondrocytes
Authors: Embry Jennifer J. , Knudson Warren 
Published: December 2003

AbstractObjectiveTo determine whether aggrecan fragments bound to hyaluronan (HA) can be retained and internalized by articular chondrocytes and whether these events are dependent on HA and its receptor, CD44. An additional objective was to determine whether partial degradation of aggrecan is a prerequisite for internalization.MethodsBinding and internalization of a variety of fluorescein isothiocyanate (FITC)– or biotin‐labeled HA/proteoglycan probes were investigated on normal bovine articular cartilage chondrocytes, bovine articular chondrocytes transfected with a dominant‐negative construct of CD44, or COS‐7 cells transfected with wild‐type CD44. The probes were defined as being internalized by the presence of label associated with the cells following extensive trypsinization of the cell surface.ResultsBiotinylated aggrecan fragments bound to FITC‐HA were cointernalized in bovine articular chondrocytes or COS‐7 cells transfected with CD44. Intracellular vesicles containing FITC‐HA colocalized with a fluorescent probe for lysosomes. The internalization of the aggrecan fragments was dependent on the presence of HA as well as the presence of functional CD44. Intact aggrecan/FITC‐HA complexes bound to the cell surface but were not internalized. However, following brief trypsin digestion of the aggrecan/HA complex, the remaining proteoglycan fragments were bound and internalized.ConclusionPartially degraded aggrecan fragments (e.g., aggrecan G1 domains bound to HA) can be internalized by articular chondrocytes via a mechanism involving HA/CD44‐mediated endocytosis. Further, the presence of an intact aggrecan monomer bound to HA inhibits the internalization of HA as well as HA‐bound fragments.
Reduction of osteophyte formation and synovial thickening by adenoviral overexpression of transforming growth factor β/bone morphogenetic protein inhibitors during experimental osteoarthritis
Authors: Scharstuhl Alwin , Vitters Elly L. , van der Kraan Peter M. , van den Berg Wim B. 
Published: December 2003

AbstractObjectiveOsteoarthritis (OA) is a joint disease characterized by osteophyte development, fibrosis, and articular cartilage damage. Effects of exogenous transforming growth factor β (TGFβ) isoforms and bone morphogenetic proteins (BMPs) suggest a role for these growth factors in the pathogenesis of OA. The aim of this study was to elucidate the role of endogenous TGFβ and BMP during papain‐induced OA‐like changes in mice.MethodsWe used adenoviral overexpression of TGFβ and BMP antagonists to block growth factor signaling. An adenovirus expressing a secreted, pan–specific TGFβ antagonist called murine latency‐associated peptide 1 (mLAP‐1) was used. In addition, we used intracellular inhibitory Smad6 as a BMP antagonist and Smad7 as a TGFβ/BMP inhibitor. Papain was injected into the knee joints of C57BL/6 mice to induce osteophyte development, synovial thickening, and articular cartilage proteoglycan (PG) loss.ResultsIntraarticular injection of papain caused increased protein expression of several TGFβ and BMP isoforms in synovium and cartilage. Adenovirus transfection into the joint resulted in a strong expression of the transgenes in the synovial lining. Overexpression of mLAP‐1, Smad6, and Smad7 led to a significant reduction in osteophyte formation compared with that in controls. Smad6 and Smad7 overexpression also significantly decreased synovial thickening. Furthermore, the secreted TGFβ inhibitor mLAP‐1 increased articular cartilage PG loss.ConclusionOur results indicate a pivotal role of endogenous TGFβ in the development of osteophytes and synovial thickening, implicating endogenous TGFβ in the pathogenesis of OA. In contrast, the prevention of cartilage damage by endogenous TGFβ signifies the protective role of TGFβ in articular cartilage. This is the first study to demonstrate that endogenous BMPs are involved in osteophyte formation and synovial thickening in experimental OA.
Oncostatin M in combination with tumor necrosis factor α induces cartilage damage and matrix metalloproteinase expression in vitro and in vivo
Authors: Hui W. , Rowan A. D. , Richards C. D. , Cawston T. E. 
Published: December 2003

AbstractObjectiveTo determine the effects of the proinflammatory cytokine combination of oncostatin M (OSM) and tumor necrosis factor α (TNFα) on cartilage destruction in both in vitro and in vivo model systems.MethodsThe release of collagen and proteoglycan was assessed in bovine cartilage explant cultures, while messenger RNA (mRNA) from bovine chondrocytes was analyzed by Northern blotting. Immunohistochemistry was performed on sections prepared from murine joints following injection of adenovirus vectors encoding murine OSM and/or murine TNFα.ResultsThe combination of OSM + TNFα induced significant collagen release from bovine cartilage, accompanied by high levels of active collagenolytic activity. Northern blot analysis indicated that this cytokine combination synergistically induced matrix metalloproteinase 1 (MMP‐1), MMP‐3, and MMP‐13 mRNA. The in vivo data clearly indicated that OSM + TNFα overexpression increased MMP levels and decreased levels of tissue inhibitor of metalloproteinases 1 (TIMP‐1). Specifically, OSM + TNFα induced marked synovial hyperplasia, inflammation, and cartilage and bone destruction with a concomitant increase in MMP expression in both cartilage and synovium and decreased TIMP‐1 expression in the articular cartilage. These effects were markedly greater than those seen with either cytokine alone.ConclusionThis study demonstrates that OSM + TNFα represents a potent proinflammatory cytokine combination that markedly induces MMP production in both cartilage and synovium, thus promoting joint destruction.
Prognostic factors for radiographic progression, radiographic damage, and disability in juvenile idiopathic arthritis
Authors: Magni‐Manzoni Silvia , Rossi Federica , Pistorio Angela , Temporini Francesca , Viola Stefania , Beluffi Giampiero , Martini Alberto , Ravelli Angelo 
Published: December 2003

AbstractObjectiveTo investigate the rate of radiographic progression and identify prognostic factors of radiographic progression, radiographic damage, and physical disability in juvenile idiopathic arthritis (JIA).MethodsNinety‐four JIA patients with a median disease duration of 1.1 years were followed up prospectively for a median of 4.5 years. Bilateral wrist radiographs were obtained at baseline, at 1 year, and at the last followup visit. Radiographic damage was assessed by the carpal length (Poznanski score), and physical disability by the Childhood Health Assessment Questionnaire (C‐HAQ). Yearly radiographic progression, the Poznanski score at the final visit, and the C‐HAQ score at the final visit were used as outcome measures. Baseline parameters included demographic, clinical, laboratory, and radiographic data.ResultsThe mean ± SD Poznanski score was −1.2 ± 1.3 at baseline, −1.7 ± 1.8 at the 1‐year visit, and −1.9 ± 2.2 at the final visit (P < 0.0001). Radiographic progression was greater during the first year (mean ± SD −0.5 ± 1.1) than between the 1‐year visit and the final visit (−0.2 ± 1.3). The mean yearly radiographic progression during the entire study period was −0.1 ± 0.4. Logistic regression analysis revealed that radiographic progression during the first year was the only baseline parameter that was predictive of all 3 study outcomes. The final Poznanski score was also predicted by the baseline Poznanski score, whereas female sex was protective against radiographic progression.ConclusionWe identified the prognostic factors for poorer outcome in polyarticular‐course JIA. The changes in the early Poznanski score can be used to predict long‐term joint damage and physical disability.
Patterns of interphalangeal hand joint involvement of osteoarthritis among men and women: A British cohort study
Authors: Poole Jason , Sayer Avan Aihie , Hardy Rebecca , Wadsworth Michael , Kuh Diana , Cooper Cyrus 
Published: December 2003

AbstractObjectiveTo characterize the pattern of involvement of osteoarthritis (OA) of the hand among men and women of the same age.MethodsStructured hand examinations were performed on 1,467 men and 1,519 women who were age 53 years and born in England, Scotland, or Wales during the first week of March 1946 (identified through the United Kingdom National Survey of Health and Development). OA at each joint site was characterized using a previously validated examination schedule. The interrelationship of involvement of different hand joints was analyzed by logistic regression and cluster analyses.ResultsThere was clear evidence of polyarticular involvement in the hand joints of both the men and the women. Among the women, 161 subjects had ≥4 joints involved, compared with only 41 subjects expected in this category (P < 0.001). Among the men, 87 subjects were observed to have ≥4 joints involved, in contrast with only 7 subjects expected (P < 0.001). The pattern of hand joint involvement (characterized by clustering primarily by row and symmetric joint involvement, rather than clustering by ray) was found to be almost identical between the men and the women.ConclusionThis study confirms the existence of a polyarticular subset of OA among men that has characteristics similar to those of the variant observed among women. The data suggest that the genetic or metabolic influences underlying this particular variant of OA acts similarly in both sexes.
Molecular phenotyping of human chondrocyte cell lines T/C‐28a2, T/C‐28a4, and C‐28/I2
Authors: Finger F. , Schörle C. , Zien A. , Gebhard P. , Goldring M. B. , Aigner T. 
Published: December 2003

AbstractObjectiveBecause the immortalized chondrocyte cell lines C‐28/I2, T/C‐28a2, and T/C‐28a4 have become a common tool in cartilage research, permitting investigations in a largely unlimited and standardized manner, we investigated the molecular phenotype of these cell lines by gene expression profiling.MethodsComplementary DNA–array analysis as well as online quantitative polymerase chain reaction were used to identify the gene expression profiles of the 3 cell lines cultured in monolayer and alginate beads, as compared with the expression profiles of cultured human adult primary chondrocytes.ResultsA similar, but not identical, gene expression profile was established for all 3 cell lines. SOX9 was expressed at a significant level in all 3 cell lines. Extracellular matrix proteins and matrix‐degrading proteases were rarely expressed. In contrast, genes involved in the cell cycle were strongly up‐regulated, as compared with the expression levels in physiologic chondrocytes.ConclusionThe expression of SOX9, the master gene of chondrocytic cell differentiation, reflects the basically chondrocytic phenotype of these cells. However, the major issue appears to be that these cell lines mainly proliferate and show less expression of genes involved in matrix synthesis and turnover. In this respect, C‐28/I2 cells display the highest levels of matrix‐anabolic and matrix‐catabolic genes and thus are presumably preferable for use in investigating chondrocyte anabolic and catabolic activity and its regulation. None of the 3 cell lines appears to be a direct substitute for primary chondrocytes. A successful approach will have to validate the findings obtained with chondrocyte cell lines by using primary chondrocytes or cartilage‐tissue cultures. This would permit the establishment of reproducible in vitro models and subsequently allow investigators to relate the findings to the physiologic situation.
The genetic control of rheumatoid factor production in a rat model of rheumatoid arthritis
Authors: Wernhoff Patrik , Olofsson Peter , Holmdahl Rikard 
Published: December 2003

AbstractObjectiveTo investigate the genetic regulation of rheumatoid factor (RF) in a rat model of rheumatoid arthritis, in order to gain understanding of the enigmatic role of RF in the disease.MethodsIgM‐RF and IgG‐RF, as well as total levels of immunoglobulins of different subclasses, were measured in sera from rats with pristane‐induced arthritis (PIA). The major gene regions were identified by linkage analysis of genetically segregating crosses.ResultsThe production of RF was found to correlate with development of arthritis and to be higher in females than in males. Surprisingly, the relatively arthritis‐resistant E3 strain had higher levels of RF than the arthritis‐susceptible DA strain. In an (E3 × DA)F2 cohort a major locus controlling the levels of IgM‐RF in serum was identified on chromosome 11 (Rf1) and another on chromosome 16 (Rf3), and these were not related to arthritis susceptibility. However, the Rf2 locus on chromosome 4 controlled IgG‐RF levels, IgG2a levels, and chronic arthritis in males (Pia5). Some previously defined arthritis loci (Pia4, Pia6, Pia7, and Pia8) were found to also control immunoglobulin levels in serum.ConclusionRFs are produced in the rat PIA model and correlate with development of arthritis. Gene regions controlling RF and serum immunoglobulin levels were identified, of which some cosegregated with arthritis. This suggests a new focus of study to elucidate the role of RF in the pathogenesis of arthritis.
Antiidiotypic antibodies neutralize autoantibodies that inhibit cholinergic neurotransmission
Authors: Cavill Dana , Waterman Sally A. , Gordon Tom P. 
Published: December 2003

AbstractObjectiveFunctional autoantibodies that inhibit M3 muscarinic receptor (M3R)–mediated neurotransmission have been reported in patients with Sjögren's syndrome (SS) and in patients with scleroderma. Because of limited reports that intravenous immunoglobulin (IVIG) improves dysautonomia in primary SS, we investigated whether IVIG neutralizes the effect of anti‐M3R antibodies on colon smooth muscle contractions, in an in vitro functional assay.MethodsIgG obtained from patients with primary SS, patients with rheumatoid arthritis and secondary SS, and patients with scleroderma was tested, before and after coincubation with equimolar amounts of IVIG or its F(ab′)2 and Fc fractions, for the ability to inhibit carbachol‐evoked colon smooth muscle contractions. In addition, patient IgG was passed through an IVIG F(ab′)2 column, and unretained IgG was tested for functional activity on colon smooth muscle strips. Purified IgG obtained from healthy adults was also examined for a neutralizing effect on anti‐M3R antibody activity.ResultsInhibition of colon contractions was mediated by the Fab fraction of patient IgG. Coincubation of IgG from the 3 patient groups with IVIG or its F(ab′)2 fragment neutralized anti‐M3R antibody–mediated inhibition of cholinergic smooth muscle contractions. Preabsorption of patient IgG with Sepharose‐bound IVIG F(ab′)2 removed the anti‐M3R inhibitory activity. In addition, purified IgG from each of 4 healthy adults neutralized the functional autoantibodies.ConclusionAnti‐M3R antibody activity does not require receptor crosslinking. Antiidiotypic antibodies present in pooled IgG neutralize patient IgG–mediated inhibition of M3R cholinergic neurotransmission, providing a rationale for IVIG as a treatment of autonomic dysfunction in patients with SS and patients with scleroderma. Furthermore, antiidiotypic antibodies in healthy individuals may prevent the emergence of pathogenic anti‐M3R autoantibodies.