bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metallvinylidene und ‐allenylidene in der Katalyse
Authors: Bruneau Christian , Dixneuf Pierre H. 
Published: March 2006

AbstractDas Auftreten einer katalytischen Metallvinylidenspezies wurde erstmals im Jahre 1986 vorgeschlagen, um die direkte regioselektive Bildung von Vinylcarbamaten aus terminalen Alkinen, Kohlendioxid und Aminen zu erklären. Seit diesem ersten Bericht haben sich diverse Metallvinylidene und Metallallenylidene, die die Schlüsselintermediate bei der Aktivierung sind, als sehr nützliche Reagentien für viele Alkinreaktionen erwiesen und außerdem zum gezielten Entwurf von neuen katalytischen Reaktionen beigetragen. Derweil sich diese Entdeckung nun zum zwanzigsten Male jährt, scheint der Zeitpunkt geeignet, auf die Fortschritte zurückzublicken, die seither bei der Anwendung von metallorganischen Vinylidenen und Allenylidenen in der Katalyse erzielt worden sind.
Metal Vinylidenes and Allenylidenes in Catalysis: Applications in Anti‐Markovnikov Additions to Terminal Alkynes and Alkene Metathesis
Authors: Bruneau Christian , Dixneuf Pierre H. 
Published: March 2006

AbstractThe involvement of a catalytic metal vinylidene species was proposed for the first time in 1986 to explain the regioselective formation of vinyl carbamates directly from terminal alkynes, carbon dioxide, and amines. Since this initial report, various metal vinylidenes and allenylidenes, which are key activation intermediates, have proved extremely useful for many alkyne transformations. They have contributed to the rational design of new catalytic reactions. This 20th anniversary is a suitable occasion to present the advancement of organometallic vinylidenes and allenylidenes in catalysis.
Deiminated Epstein‐Barr virus nuclear antigen 1 is a target of anti–citrullinated protein antibodies in rheumatoid arthritis
Authors: Pratesi Federico , Tommasi Cristina , Anzilotti Consuelo , Chimenti Daniele , Migliorini Paola 
Published: February 2006

AbstractObjectiveTo test the hypothesis that deimination of viral sequences containing Arg–Gly repeats could generate epitopes recognized by anti–citrullinated protein antibodies (ACPAs) that are present in rheumatoid arthritis (RA) sera.MethodsMultiple antigen peptides derived from Epstein‐Barr virus (EBV)–encoded Epstein‐Barr nuclear antigen 1 (EBNA‐1) were synthesized, substituting the arginines with citrulline, and were used to screen RA sera. Anti–cyclic citrullinated peptide antibodies were purified by affinity chromatography and tested on a panel of in vitro deiminated proteins. Their ability to bind in vivo deiminated proteins was evaluated by immunoprecipitation, using EBV‐infected cell lines.ResultsAntibodies specific for a peptide corresponding to the EBNA‐135–58 sequence containing citrulline in place of arginine (viral citrullinated peptide [VCP]) were detected in 50% of RA sera and in <5% of normal and disease control sera. In addition, affinity‐purified anti‐VCP antibodies from RA sera reacted with filaggrin‐derived citrullinated peptides, with deiminated fibrinogen, and with deiminated recombinant EBNA‐1. Moreover, anti‐VCP antibodies immunoprecipitated, from the lysate of calcium ionophore–stimulated lymphoblastoid cell lines, an 80‐kd band that was reactive with a monoclonal anti–EBNA‐1 antibody and with anti–modified citrulline antibodies.ConclusionThese data indicate that ACPAs react with a viral deiminated protein and suggest that EBV infection may play a role in the induction of these RA‐specific antibodies.
Hypermethylated promoter region of DR3, the death receptor 3 gene, in rheumatoid arthritis synovial cells
Authors: Takami Nozomi , Osawa Kayo , Miura Yasushi , Komai Koichiro , Taniguchi Mariko , Shiraishi Masahiko , Sato Keizo , Iguchi Tetsuhiro , Shiozawa Kazuko , Hashiramoto Akira , Shiozawa Shunichi 
Published: February 2006

AbstractObjectiveTo examine the promoter activity and protein expression of the death receptor 3 gene DR3, a member of the apoptosis‐inducing Fas gene family, with particular reference to the methylation status of its promoter region in rheumatoid arthritis (RA).MethodsGenomic DNA was prepared from peripheral blood mononuclear cells obtained from healthy individuals and from patients with RA and synovial cells obtained from patients with RA and osteoarthritis. The methylation status of the DR3 promoter was analyzed by bisulfite genomic sequencing and methylation‐specific polymerase chain reaction techniques. Gene promoter activity and protein expression were examined using the luciferase reporter and Western blotting techniques.ResultsThe promoter region of the DR3 gene contained many CpG motifs, including one CpG island that was specifically hypermethylated in synovial cells from patients with RA. Promoter assays showed that the promoter CpG island was essential for the transactivation of the DR3 gene and that forced hypermethylation of the CpG island with the bacterial methylase Sss I in vitro resulted in inhibition of the DR3 gene expression. Furthermore, the expression of DR‐3 protein was down‐modulated in association with methylation of the promoter CpG island in RA synovial cells.ConclusionThe CpG island in the DR3 gene promoter was specifically methylated to down‐modulate the expression of DR‐3 protein in rheumatoid synovial cells, which may provide resistance to apoptosis in RA synovial cells.
Comparative analysis of gene expression profiles in intact and damaged regions of human osteoarthritic cartilage
Authors: Sato Tomoo , Konomi Koji , Yamasaki Satoshi , Aratani Satoko , Tsuchimochi Kaneyuki , Yokouchi Masahiro , Masuko‐Hongo Kayo , Yagishita Naoko , Nakamura Hiroshi , Komiya Setsuro , Beppu Moroe , Aoki Haruhito , Nishioka Kusuki , Nakajima Toshihiro 
Published: February 2006

AbstractObjectiveTo analyze the differences in gene expression profiles of chondrocytes in intact and damaged regions of cartilage from the same knee joint of patients with osteoarthritis (OA) of the knee.MethodsWe compared messenger RNA expression profiles in regions of intact and damaged cartilage (classified according to the Mankin scale) obtained from patients with knee OA. Five pairs of intact and damaged regions of OA cartilage were evaluated by oligonucleotide array analysis using a double in vitro transcription amplification technique. The microarray data were confirmed by real‐time quantitative polymerase chain reaction (PCR) amplification and were compared with previously published data.ResultsAbout 1,500 transcripts, which corresponded to 8% of the expressed transcripts, showed ≥2‐fold differences in expression between the cartilage tissue pairs. Approximately 10% of these transcripts (n = 151) were commonly expressed in the 5 patient samples. Accordingly, 114 genes (35 genes expressed in intact > damaged; 79 genes expressed in intact < damaged) were selected. The expression of some genes related to the wound‐healing process, including cell proliferation and interstitial collagen synthesis, was higher in damaged regions than in intact regions, similar to the findings for genes that inhibit matrix degradation. Comparisons of the real‐time quantitative PCR data with the previously reported data support the validity of our microarray data.ConclusionDifferences between intact and damaged regions of OA cartilage exhibited a similar pattern among the 5 patients examined, indicating the presence of common mechanisms that contribute to cartilage destruction. Elucidation of this mechanism is important for the development of effective treatments for OA.
Catabolic stress induces features of chondrocyte senescence through overexpression of caveolin 1: Possible involvement of caveolin 1–induced down‐regulation of articular chondrocytes in the pathogenesis of osteoarthritis
Authors: Dai Sheng‐Ming , Shan Zheng‐Zheng , Nakamura Hiroshi , Masuko‐Hongo Kayo , Kato Tomohiro , Nishioka Kusuki , Yudoh Kazuo 
Published: February 2006

AbstractObjectiveArticular chondrocyte senescence is responsible, at least in part, for the increased incidence of osteoarthritis (OA) with increased age. Recently, it was suggested that caveolin 1, a 21–24‐kd membrane protein, participates in premature cellular senescence. Caveolin 1 is the principal structural component of caveolae, vesicular invaginations of the plasma membrane. This study was undertaken to investigate whether the catabolic factors oxidative stress and interleukin‐1β (IL‐1β) induce features of premature senescence of articular chondrocytes through up‐regulation of caveolin 1 expression.MethodsCaveolin 1 expression was investigated in human OA cartilage by real‐time polymerase chain reaction and in rat OA cartilage by immunohistologic analysis. We studied whether IL‐1β and H2O2 induce caveolin 1 expression in OA chondrocytes and analyzed the relationship between cellular senescent phenotypes and caveolin 1 expression in human chondrocytes.ResultsIn human and rat OA articular cartilage, caveolin 1 positivity was associated with cartilage degeneration. Both IL‐1β and H2O2 up‐regulated caveolin 1 messenger RNA and protein levels, and both treatments induced marked expression of senescent phenotypes: altered cellular morphology, cell growth arrest, telomere erosion, and specific senescence‐associated β‐galactosidase activity. Caveolin 1 overexpression induced p38 MAPK activation and impaired the ability of chondrocytes to produce type II collagen and aggrecan. In contrast, down‐regulation of caveolin 1 with antisense oligonucleotide significantly inhibited the features of chondrocyte senescence induced by catabolic factors. Caveolin 1 induction and stresses with both IL‐1β and H2O2 up‐regulated p53 and p21 and down‐regulated phosphorylated retinoblastoma (Rb), suggesting that the p53/p21/Rb phosphorylation pathway, as well as prolonged p38 MAPK activation, may mediate the features of chondrocyte senescence induced by stress.ConclusionOur findings suggest that IL‐1β and oxidative stress induce features of premature senescence in OA chondrocytes, mediated, at least in part, by stress‐induced caveolin 1 expression. This indicates that caveolin 1 plays a role in the pathogenesis of OA via promotion of chondrocyte down‐regulation.
Vasoactive intestinal peptide induces CD4+,CD25+ T regulatory cells with therapeutic effect in collagen‐induced arthritis
Authors: Gonzalez‐Rey Elena , Fernandez‐Martin Amelia , Chorny Alejo , Delgado Mario 
Published: February 2006

AbstractObjectiveCD4+,CD25+ T regulatory cells (Treg) control the immune response to a variety of antigens, including self antigens, and may offer opportunities to intervene in the course of autoimmune diseases. Several models support the idea of the peripheral generation of CD4+,CD25+ Treg from CD4+,CD25− T cells, but little is known about the endogenous factors and mechanisms controlling the peripheral expansion of CD4+,CD25+ Treg. We undertook this study to investigate the capacity of the vasoactive intestinal peptide (VIP), an immunosuppressive antiarthritic neuropeptide, to induce functional Treg in vivo during the development of collagen‐induced arthritis (CIA).MethodsWe measured the number of CD4+,CD25+ Treg following VIP administration to CIA mice, and we characterized their phenotype and their ability to suppress activation of autoreactive T cells. We determined the capacity of VIP to induce Treg in vitro as well as the use of Treg in the treatment of CIA, measuring the clinical evolution and the inflammatory and autoimmune components of the disease.ResultsThe administration of VIP to arthritic mice resulted in the expansion of CD4+,CD25+,Foxp3+ Treg in the periphery and joints, which inhibited autoreactive T cell activation/expansion. VIP induced more efficient suppressors on a per‐cell basis. The VIP‐generated CD4+,CD25+ Treg transfer suppressed and significantly ameliorated the progression of the disease.ConclusionThese results demonstrate the involvement of the generation of Treg in the therapeutic effect of VIP on CIA. The generation of highly efficient Treg by VIP ex vivo could be used as an attractive therapeutic tool in the future, avoiding the administration of the peptide to patients with rheumatoid arthritis.
Involvement of phosphatidylserine, αvβ3, CD14, CD36, and complement C1q in the phagocytosis of primary necrotic lymphocytes by macrophages
Authors: Böttcher Andrea , Gaipl Udo S. , Fürnrohr Barbara G. , Herrmann Martin , Girkontaite Irute , Kalden Joachim R. , Voll Reinhard E. 
Published: February 2006

AbstractObjectiveUningested dead cells may be an important source of autoantigens and may trigger autoimmune diseases such as systemic lupus erythematosus (SLE). Multiple receptors involved in the clearance of apoptotic cells have been described; however, little is known about the receptors and ligands involved in uptake of necrotic cells that release autoantigens as well.MethodsThe uptake of autologous necrotic peripheral blood lymphocytes into human monocyte‐derived macrophages was qualitatively and quantitatively monitored by confocal microscopy and 2‐color flow cytometry, respectively. Blocking experiments were performed to examine the receptors and molecules involved in the phagocytosis of necrotic cells. Cytokine secretion by lipopolysaccharide‐activated monocytes and macrophages was determined by enzyme‐linked immunosorbent assay.ResultsPhosphatidylserine, which was exposed on necrotic as well as apoptotic cells, promoted the recognition and removal of primary necrotic lymphocytes. Several macrophage receptor systems, including the thrombospondin–CD36–αvβ3 complex, CD14, and the complement component C1q, contributed to the engulfment of necrotic cells. Necrotic peripheral blood lymphocytes slightly increased the lipopolysaccharide‐induced secretion of interleukin‐10 and reduced the secretion of tumor necrosis factor α in monocytes and macrophages.ConclusionOur results indicate that at least some of the receptors and adaptors mediating the uptake of apoptotic cells are also involved in the clearance of necrotic cells. Hence, necrotic cells engage phagocyte receptors such as CD36, which mediate antiinflammatory signals from apoptotic cells. Necrotic cells consequently also have the potency to provide antiinflammatory signals to phagocytes; however, these signals may be overridden by proinflammatory factors released during necrosis. These findings have implications regarding the etiopathogenesis of autoimmune diseases such as SLE, in which impaired clearance of dead cells may foster autoimmunity by the release of potential autoantigens.
Obstetric hospitalizations in the United States for women with systemic lupus erythematosus and rheumatoid arthritis
Authors: Chakravarty Eliza F. , Nelson Lorene , Krishnan Eswar 
Published: February 2006

AbstractObjectiveTo estimate the national occurrence of pregnancies in women with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) and to compare pregnancy outcomes in these patients with those in women with pregestational diabetes mellitus (DM) and with the general obstetric population.MethodsWe studied the 2002 Nationwide Inpatient Sample of the Healthcare Cost and Utilization Project to estimate the number of obstetric hospitalizations, deliveries, and cesarean deliveries in women with SLE, RA, pregestational DM, and the general obstetric population. Pregnancy outcomes included length of hospital stay, hypertensive disorders including preeclampsia, premature rupture of membranes, and intrauterine growth restriction.ResultsOf an estimated 4.04 million deliveries, 3,264 occurred in women with SLE, 1,425 in women with RA, and 13,574 in women with pregestational DM. Women with SLE, RA, and pregestational DM had significantly increased rates of hypertensive disorders compared with the general obstetric population (23.2%, 11.1%, 27.4%, and 7.8%, respectively), longer hospital stays, and significantly higher risk of cesarean delivery. Although women with SLE, RA, and pregestational DM were significantly older than women in the general obstetric population, disparities in the risk of adverse outcomes of pregnancy remained statistically significant after adjustment for maternal age.ConclusionTo our knowledge, this is the first study to examine national data on pregnancy outcomes in women with common rheumatic diseases. As with underlying pregestational DM, women with SLE and RA appear to have a higher age‐adjusted risk of adverse outcomes of pregnancy and longer hospital stays than do pregnant women in the general population, and careful antenatal monitoring should be performed.
The association of meniscal pathologic changes with cartilage loss in symptomatic knee osteoarthritis
Authors: Hunter D. J. , Zhang Y. Q. , Niu J. B. , Tu X. , Amin S. , Clancy M. , Guermazi A. , Grigorian M. , Gale D. , Felson D. T. 
Published: February 2006

AbstractObjectiveTo explore the role of meniscal tears and meniscal malposition as risk factors for subsequent cartilage loss in subjects with symptomatic osteoarthritis (OA).MethodsStudy subjects were patients with symptomatic knee OA from the Boston Osteoarthritis of the Knee Study. Baseline assessments included knee magnetic resonance imaging (MRI) with followup MRI at 15 and 30 months. Cartilage and meniscal damage were scored on MRI in the medial and lateral tibiofemoral joints using the semiquantitative whole‐organ magnetic resonance imaging score. Tibiofemoral cartilage was scored on MR images of all 5 plates of each tibiofemoral joint, and the meniscal position was measured using eFilm Workstation software. A proportional odds logistic regression model with generalized estimating equations was used to assess the effect of each predictor (meniscal position factor and meniscal damage as dichotomous predictors in each model) on cartilage loss in each of the 5 plates within a compartment. Models were adjusted for age, body mass index (BMI), tibial width, and sex.ResultsWe assessed 257 subjects whose mean ± SD age was 66.6 ± 9.2 years and BMI was 31.5 ± 5.7 kg/m2; 42% of subjects were female, and 77% of knees had a Kellgren/Lawrence radiographic severity grade ≥2. In the medial tibiofemoral joint, each measure of meniscal malposition was associated with an increased risk of cartilage loss. There was also a strong association between meniscal damage and cartilage loss. Since meniscal coverage and meniscal height diminished with subluxation, less coverage and reduced height also increased the risk of cartilage loss.ConclusionThis study highlights the importance of an intact and functioning meniscus in patients with symptomatic knee OA, since the findings demonstrate that loss of this function has important consequences for cartilage loss.
2‐(N‐Fmoc)‐3‐(N‐Boc‐N‐methoxy)‐diaminopropanoic acid, an amino acid for the synthesis of mimics of O‐linked glycopeptides
Authors: Carrasco Michael R. , Brown Ryan T. , Doan Vu H. , Kandel Sean M. , Lee Franklin C. 
Published: February 2006

AbstractAmino acids with N‐alkylaminooxy side chains have proven effective for the rapid synthesis of neoglycopeptides. Chemoselective reaction of reducing sugars with peptides containing these amino acids provides glycoconjugates that are structurally similar to their natural counterparts. 2‐(N‐Fmoc)‐3‐(N‐Boc‐N‐methoxy)‐diaminopropanoic acid (Fmoc: 9‐fluorenylmethoxycarbonyl; Boc: t‐butyloxycarbonyl) was synthesized from Boc–Ser–OH in >40% overall yield and incorporated into peptides by standard Fmoc chemistry based solid phase peptide synthesis. The resulting peptides are efficiently glycosylated and serve as mimics of O‐linked glycopeptides. The synthesis of this derivative greatly expands the availability of the N‐alkylaminooxy strategy for neoglycopeptides. © 2006 Wiley Periodicals, Inc. Biopolymers(Pept Sci) 84: 414–420, 2006This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
Restrained molecular dynamics simulations of HIV‐1 protease: The first step in validating a new target for drug design
Authors: Perryman Alexander L. , Lin Jung‐Hsin , McCammon J. Andrew 
Published: February 2006

AbstractTo test the anticorrelated relationship that was recently displayed in conventional molecular dynamics (MD) simulations, several different restrained MD simulations on a wild type and on the V82F/I84V drug‐resistant mutant of HIV‐1 protease were performed. This anticorrelated relationship refers to the observation that compression of the peripheral ear‐to‐cheek region of HIV protease (i.e., the elbow of the flap to the fulcrum and the cantilever) occurred as the active site flaps were opening, and, conversely, expansion of that ear‐to‐cheek region occurred as both flaps were closing. An additional examination of this anticorrelated relationship was necessary to determine whether it can be harnessed in a useful manner. Consequently, six different MD experiments were performed that incorporated pairwise distance restraints in that ear‐to‐cheek region (i.e., the distance between the α‐carbons of Gly40 and Gln61 was restrained to either 7.7 or 10.5 Å, in both monomers). Pushing the backbones of the ear and the cheek regions away from each other slightly did force the flaps that guard the active site to remain closed in both the wild type and the mutant systems—even though there were no ligands in the active sites. Thus, these restrained MD simulations provided evidence that the anticorrelated relationship can be exploited to affect the dynamic behavior of the flaps that guard the active site of HIV‐1 protease. These simulations supported our hypothesis of the mechanism governing flap motion, and they are the first step towards validating that peripheral surface as a new target for drug design. © 2006 Wiley Periodicals, Inc. Biopolymers 82: 272–284, 2006This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
Spatial patterns of protein expression in focal infections of human cytomegalovirus
Authors: Lam Vy , Boehme Karl W. , Compton Teresa , Yin John 
Published: February 2006

AbstractHuman cytomegalovirus (HCMV) is a medically significant human pathogen that infects a wide range of cell and tissue types. During infection, HCMV activates a variety of signal transduction pathways that induce profound changes in cellular processes and dramatically affect cellular gene expression patterns. To better define how these virus‐host interactions affect the local microenvironment and influence the spatial and temporal spread of HCMV, we initiated HCMV focal infections on normal human dermal fibroblast monolayers and monitored viral gene expression patterns and infection spread over 45 days. To establish baseline temporal measurements of HCMV infection and spread in cell monolayers, we characterized the influence of three experimental variables on viral gene expression: cell plating density, the presence of serum, and neutralization of cellular antiviral responses with an antibody against interferon‐β. We found that high cell plating density or the inclusion of serum correlated with enhanced HCMV infection spread. Dramatic differences in the expression pattern of the viral immediate early 2 (IE2) gene were observed under these conditions as compared to low plating density or the absence of serum. In the latter case round, uniform foci were observed with a clear wave of IE2 expression visible in advance of a late stage viral protein, envelope glycoprotein B. By contrast, larger irregular foci with arms of IE2 expression were observed in the presence of serum. Addition of the antibody had little effect on the rate of spread, which is consistent with the knowledge that HCMV represses antiviral responses during infection. This experimental system provides a useful means to visualize and quantify complex virus‐host interactions. © 2006 Wiley Periodicals, Inc.