bluuebunny/crossref_metadata_2025_split huggingface dataset:
Classification, presentation, and initial treatment of Wegener's granulomatosis in childhood
Authors: Cabral David A. , Uribe América G. , Benseler Susanne , O'Neil Kathleen M. , Hashkes Philip J. , Higgins Gloria , Zeft Andrew S. , Lovell Daniel J. , Kingsbury Daniel J. , Stevens Anne , McCurdy Deborah , Chira Peter , Abramson Leslie , Arkachaisri Thaschawee , Campillo Sarah , Eberhard Anne , Hersh Aimee O. , Huber Adam M. , Kim Susan , Klein‐Gitelman Marisa , Levy Deborah M. , Li Suzanne C. , Mason Thomas , DeWitt Esi Morgan , Muscal Eyal , Nassi Lorien , Reiff Andreas , Schikler Kenneth , Singer Nora G. , Wahezi Dawn , Woodward Amy 
Published: October 2009

AbstractObjectiveTo compare the criteria for Wegener's granulomatosis (WG) of the American College of Rheumatology (ACR) with those of the European League Against Rheumatism/Pediatric Rheumatology European Society (EULAR/PRES) in a cohort of children with WG and other antineutrophil cytoplasmic antibody (ANCA)–associated vasculitides (AAVs), and to describe the interval to diagnosis, presenting features, and initial treatment for WG.MethodsEligible patients had been diagnosed by site rheumatologists (termed the “MD diagnosis”) since 2004. This diagnosis was used as a reference standard for sensitivity and specificity testing of the 2 WG classification criteria. Descriptive analyses were confined to ACR‐classified WG patients.ResultsMD diagnoses of 117 patients (82 of whom were female) were WG (n = 76), microscopic polyangiitis (n = 17), ANCA‐positive pauci‐immune glomerulonephritis (n = 5), Churg‐Strauss syndrome (n = 2), and unclassified vasculitis (n = 17). The sensitivities of the ACR and EULAR/PRES classification criteria for WG among the spectrum of AAVs were 68.4% and 73.6%, respectively, and the specificities were 68.3% and 73.2%, respectively. Two more children were identified as having WG by the EULAR/PRES criteria than by the ACR criteria. For the 65 ACR‐classified WG patients, the median age at diagnosis was 14.2 years (range 4–17 years), and the median interval from symptom onset to diagnosis was 2.7 months (range 0–49 months). The most frequent presenting features by organ system were constitutional (89.2%), pulmonary (80.0%), ear, nose, and throat (80.0%), and renal (75.4%). Fifty‐four patients (83.1%) commenced treatment with the combination of corticosteroids and cyclophosphamide, with widely varying regimens; the remainder received methotrexate alone (n = 1), corticosteroids alone (n = 4), or a combination (n = 6).ConclusionThe EULAR/PRES criteria minimally improved diagnostic sensitivity and specificity for WG among a narrow spectrum of children with AAVs. Diagnostic delays may result from poor characterization of childhood WG. Initial therapy varied considerably among participating centers.
DNA demethylation at specific CpG sites in the IL1B promoter in response to inflammatory cytokines in human articular chondrocytes
Authors: Hashimoto Ko , Oreffo Richard O. C. , Gibson Marc B. , Goldring Mary B. , Roach Helmtrud I. 
Published: October 2009

AbstractObjectiveTo determine whether changes in the DNA methylation status in the promoter region of the gene encoding interleukin‐1β (IL‐1β) account for expression of IL1B messenger RNA (mRNA) after long‐term treatment of human articular chondrocytes with inflammatory cytokines.MethodsIL‐1β, tumor necrosis factor α (TNFα) plus oncostatin M (OSM), or 5‐azadeoxycytidine (5‐aza‐dC) was added twice weekly for 4–5 weeks to primary cultures of normal human articular chondrocytes derived from the femoral head cartilage of patients with a fracture of the femoral neck. Expression of MMP13, IL1B, TNFA, and DNMT1 was determined by SYBR Green–based quantitative reverse transcription–polymerase chain reaction (RT‐PCR) analysis of genomic DNA and total RNA extracted from the same sample before and after culture. Bisulfite modification was used to identify which CpG sites in the IL1B promoter showed differential methylation between IL1B‐expressing and IL1B‐nonexpressing cells. The percentages of cells that were methylated at that critical CpG site (–299 bp) were quantified by a method that depended on methylation‐sensitive restriction enzymes and real‐time RT‐PCR. Secretion of IL‐1β into the culture media was assessed by enzyme‐linked immunosorbent assay.ResultsHealthy chondrocytes did not express IL1B mRNA, but the levels were increased 5‐fold by treatment with 5‐aza‐dC and were increased 100–1,000‐fold by treatment with TNFα/OSM. The percentage CpG methylation was decreased by 5‐aza‐dC treatment but was reduced considerably more by IL‐1β and was almost abolished by TNFα/OSM. The mRNA was translated into protein in cytokine‐treated chondrocytes.ConclusionThese novel findings indicate that inflammatory cytokines can change the DNA methylation status at key CpG sites, resulting in long‐term induction of IL1B in human articular chondrocytes.
Macrophage activation syndrome in juvenile systemic lupus erythematosus: A multinational multicenter study of thirty‐eight patients
Authors: Parodi Alessandro , Davì Sergio , Pringe Alejandra Beatriz , Pistorio Angela , Ruperto Nicolino , Magni‐Manzoni Silvia , Miettunen Paivi , Bader‐Meunier Brigitte , Espada Graciela , Sterba Gary , Ozen Seza , Wright Dowain , Magalhães Claudia Saad , Khubchandani Raju , Michels Hartmut , Woo Patricia , Iglesias Antonio , Guseinova Dinara , Bracaglia Claudia , Hayward Kristen , Wouters Carine , Grom Alexei , Vivarelli Marina , Fischer Alberto , Breda Luciana , Martini Alberto , Ravelli Angelo 
Published: October 2009

AbstractObjectiveTo describe the clinical and laboratory features of macrophage activation syndrome as a complication of juvenile systemic lupus erythematosus (SLE).MethodsCases of juvenile SLE–associated macrophage activation syndrome were provided by investigators belonging to 3 pediatric rheumatology networks or were found in the literature. Patients who had evidence of macrophage hemophagocytosis on bone marrow aspiration were considered to have definite macrophage activation syndrome, and those who did not have such evidence were considered to have probable macrophage activation syndrome. Clinical and laboratory findings in patients with macrophage activation syndrome were contrasted with those of 2 control groups composed of patients with active juvenile SLE without macrophage activation syndrome. The ability of each feature to discriminate macrophage activation syndrome from active disease was evaluated by calculating sensitivity, specificity, and area under the receiver operating characteristic curve.ResultsThe study included 38 patients (20 with definite macrophage activation syndrome and 18 with probable macrophage activation syndrome). Patients with definite and probable macrophage activation syndrome were comparable with regard to all clinical and laboratory features of the syndrome, except for a greater frequency of lymphadenopathy, leukopenia, and thrombocytopenia in patients with definite macrophage activation syndrome. Overall, clinical features had better specificity than sensitivity, except for fever, which was highly sensitive but had low specificity. Among laboratory features, the best sensitivity and specificity was achieved using hyperferritinemia, followed by increased levels of lactate dehydrogenase, hypertriglyceridemia, and hypofibrinogenemia. Based on the results of statistical analysis, preliminary diagnostic guidelines for macrophage activation syndrome in juvenile SLE were developed.ConclusionOur findings indicate that the occurrence of unexplained fever and cytopenia, when associated with hyperferritinemia, in a patient with juvenile SLE should raise the suspicion of macrophage activation syndrome. We propose preliminary guidelines for this syndrome in juvenile SLE to facilitate timely diagnosis and correct classification of patients.
Integrated cardiac and vascular assessment in Takayasu arteritis by cardiovascular magnetic resonance
Authors: Keenan Niall G. , Mason Justin C. , Maceira Alicia , Assomull Ravi , O'Hanlon Rory , Chan Cheuk , Roughton Michael , Andrews Jacqueline , Gatehouse Peter D. , Firmin David N. , Pennell Dudley J. 
Published: October 2009

AbstractObjectiveThis study was undertaken to evaluate the value of cardiovascular magnetic resonance (CMR) in the assessment of patients with Takayasu arteritis (TA).MethodsSixteen patients with TA and 2 populations comprising 110 normal volunteers were prospectively recruited. All patients with TA underwent a CMR protocol including measurement of carotid artery wall volume, assessment of left ventricular (LV) volumes and function, and late gadolinium enhancement for the detection of myocardial scarring.ResultsCarotid artery wall volume, total vessel volume, and the wall:outer wall ratio were elevated in TA patients compared with controls (wall volume 1,045 mm3 in TA patients versus 640 mm3 in controls, P < 0.001; total vessel volume 2,268 mm3 in TA patients versus 2,037 mm3 in controls, P < 0.05; wall:outer wall ratio 48% in TA patients versus 32% in controls, P < 0.001). The lumen volume was reduced in TA (1,224 mm3 versus 1,398 mm3 in controls, P < 0.05). In TA, LV function was more dynamic, with reduced end‐systolic volume (mean ± 95% confidence interval ejection fraction 74 ± 3% versus 67 ± 1% in controls, P < 0.001; LV end‐systolic volume 19 ± 4 ml/m2 versus 25 ± 1 ml/m2 in controls, P < 0.001). Myocardial late gadolinium enhancement was present in 4 (27%) of 15 patients, indicating previously unrecognized myocardial damage.ConclusionOur findings indicate that an integrated method of cardiovascular assessment by CMR in TA not only provides good delineation of vessel wall thickening, but has also demonstrated dynamic ventricular function, myocardial scarring, and silent myocardial infarction. CMR has benefits compared with other approaches for the assessment and followup of patients with TA, and has potential to identify patients most at risk of complications, allowing early preventative therapy.
Amelioration of experimental arthritis by a telomerase‐dependent conditionally replicating adenovirus that targets synovial fibroblasts
Authors: Chen Shih‐Yao , Shiau Ai‐Li , Shieh Gia‐Shing , Su Chih‐Hau , Lee Che‐Hsin , Lee Hwei‐Ling , Wang Chrong‐Reen , Wu Chao‐Liang 
Published: October 2009

AbstractObjectiveSynovial fibroblasts (SFs) play a pivotal role in the pathogenesis of rheumatoid arthritis (RA). It has been documented that the phenotype of rheumatoid synovium is similar, in many respects, to that of an aggressive tumor. In this study, a novel, genetically engineered adenovirus was designed to lyse SFs that exhibit high telomerase activity and p53 mutations, and its effects as a novel therapeutic strategy were assessed in an experimental arthritis model.MethodsAn E1B–55‐kd–deleted adenovirus driven by the human telomerase reverse transcriptase promoter was constructed (designated Ad.GS1). Cytolysis of SFs and productive replication of Ad.GS1 in the SFs of rats with collagen‐induced arthritis (CIA), as well as the SFs of patients with RA (RASFs), were assessed in vitro and in vivo. Treatment responses, as well as the presence of disease‐related cytokines and enzymes in the ankle joints, were determined in the murine model.ResultsAd.GS1 replicated in and induced cytolysis of human RASFs and SFs from arthritic rats, but spared normal fibroblasts. Bioluminescence imaging in vivo also demonstrated replication of Ad.GS1 in arthritic rat joints, but not in normal rat joints. Intraarticular administration of Ad.GS1 significantly reduced the ankle circumference, articular index scores, radiographic scores, and histologic scores and decreased the production of interleukin‐1β, matrix metalloproteinase 9, and prolyl 4‐hydroxylase in rats with CIA compared with their control counterparts.ConclusionThis study is the first to demonstrate the amelioration of arthritic symptoms by a novel, telomerase‐dependent adenovirus in the rat CIA model, an experimental model that resembles human RA. In addition, the results suggest that because of its ability to induce cytolysis of SFs, this virus may be further explored as a therapeutic agent in patients with RA.
Increased incidence of cardiovascular events in patients with antineutrophil cytoplasmic antibody–associated vasculitides: A matched‐pair cohort study
Authors: Morgan Matthew D. , Turnbull Jennifer , Selamet Umut , Kaur‐Hayer Manvir , Nightingale Peter , Ferro Charles J. , Savage Caroline O. S. , Harper Lorraine 
Published: October 2009

AbstractObjectiveTo explore the risk of cardiovascular disease in patients with antineutrophil cytoplasmic antibody–associated vasculitides (AAVs) and to assess contributing risk factors.MethodsIn a retrospective matched‐pair cohort study, 113 of 131 patients with AAVs from a vasculitis clinic registry were matched 1:1 for renal function, age at diagnosis, sex, smoking status, and previous history of a cardiovascular disease to patients with noninflammatory chronic kidney disease (CKD). Cardiovascular events were defined as acute coronary syndrome, new‐onset angina, symptomatic peripheral vascular disease, stroke, and transient ischemic attack.ResultsMedian followup times were 3.4 years for the AAV patients and 4.2 years for the CKD patients. More cardiovascular events occurred in the AAV group (23 of 113) than in the CKD group (16 of 113). Cox regression survival analysis showed a significantly increased risk of a cardiovascular event for AAV patients, with a hazard ratio (HR) of 2.23 (95% confidence interval [95% CI] 1.1–4.4) (P = 0.017). Within the cohort of AAV patients, the most strongly predictive factors were previous history of cardiovascular disease (HR 4 [95% CI 1.7–9.8]), history of dialysis dependency (HR 4.3 [95% CI 1.5–12.1]), ever having smoked (HR 3.9 [95% CI 1.5–10]), age at diagnosis (HR 1.038 [95% CI 1.006–1.072]), estimated glomerular filtration rate at remission (HR 0.977 [95% CI 0.957–0.998]), and serum cholesterol concentration at presentation (HR 0.637 [95% CI 0.441–0.92]).ConclusionIn this retrospective study, patients with AAVs appear at greater risk of cardiovascular disease, with increased risk in those with a previous history of cardiovascular disease, dialysis dependency, poor renal function at remission, or a history of smoking. Measures to reduce the risk of cardiovascular disease should be integral to the management of systemic vasculitis.
Dorsal closure in Drosophila: cells cannot get out of the tight spot
Authors: Heisenberg Carl‐Philipp 
Published: October 2009

AbstractDorsal closure (DC), the closure of a hole in the dorsal epidermis of Drosophila embryos by the joining of opposing epithelial cell sheets, has been used as a model process to study the molecular and cellular mechanisms underlying epithelial spreading and wound healing. Recent studies have provided novel insights into how different tissues function cooperatively in this process. Specifically, they demonstrate a critical function of the epidermis surrounding the hole in modulating the behavior of the amnioserosa cells inside. These findings shed light not only on the mechanisms by which the behavior of different tissues is coordinated during DC, but also on the general mechanisms by which tissues interact to trigger global morphogenesis, an essential but yet poorly explored aspect of embryogenesis.
Liquid chromatographic–tandem mass spectrometry assay for quantitation of a novel antidiabetic S002‐853 in rat plasma and its application to pharmacokinetic study
Authors: Gautam N. , Singh R.P. , Pratap R. , Singh S.K. 
Published: October 2009

AbstractA sensitive and selective LC‐MS/MS method has been developed and validated for the estimation of novel antidiabetic synthetic flavonoid S002‐853 in rat plasma using centchroman as an internal standard. The method involves a simple two‐step liquid–liquid extraction with diethyl ether. The analyte was chromatographed on a Pierce Spheri‐5, guard cyano column (30 × 4.6  mm i.d., 5  µm) with isocratic mobile phase consisting of methanol–ammonium acetate buffer (pH 4.6, 10  mm; 90 : 10, v/v) at a flow rate of 0.75  mL/min. The API 4000 triple‐quadrupole LC–MS/MS system was operated under multiple reaction‐monitoring mode. The ionization was performed by electrospray ionization technique in positive ion mode. The chromatographic run time was 6  min and the weighted (1/x2) calibration curves were linear over the range 0.78–400  ng/mL. The limit of detection and lower limit of quantification were 0.195 and 0.78  ng/mL, respectively. The intra‐ and inter‐batch accuracy (%bias) and precision (%RSD) were found to be less than 8.47 and 11.6% respectively. The average absolute recoveries of S002‐853 and internal standard from spiked plasma samples were >90%. S002‐853 was stable for 8  h at ambient temperature, 4 weeks at −60°C and after three freeze–thaw cycles. The assay was successfully applied to determine the pharmacokinetic parameters in male Sprague–Dawley rats after an oral dose administration at 25  mg/kg. Copyright © 2009 John Wiley & Sons, Ltd.
Harsh Reaction Conditions in Continuous‐Flow Microreactors for Pharmaceutical Production
Authors: Kockmann N. , Roberge D. M. 
Published: October 2009

AbstractEnhanced transport phenomena are essential for chemical reactions in continuous‐flow microstructured equipment with transitional flow regimes. The geometry and cross‐section of the smallest channel determines the flow regime, pressure loss, and energy dissipation in the microchannel. Mixing and heat transfer are greatly influenced by the flow regime. Controlled reaction conditions lead to enhanced safety, especially for harsh reaction conditions at elevated temperatures or high concentrations. Safety and operational limits of these regimes are presented for optimized process intensification, with examples of nitration and organometallic reactions.
Iron‐Promoted ortho‐ and/or ipso‐Hydroxylation of Benzoic Acids with H2O2
Authors: Makhlynets Olga V. , Das Parthapratim , Taktak Sonia , Flook Margaret , Mas‐Ballesté Rubén , Rybak‐Akimova Elena V. , Que Lawrence 
Published: October 2009

AbstractRegioselective hydroxylation of aromatic acids with hydrogen peroxide proceeds readily in the presence of iron(II) complexes with tetradentate aminopyridine ligands [FeII(BPMEN)(CH3CN)2](ClO4)2 (1) and [FeII(TPA)(CH3CN)2](OTf)2 (2), where BPMEN=N,N′‐dimethyl‐N,N′‐bis(2‐pyridylmethyl)‐1,2‐ethylenediamine, TPA=tris‐(2‐pyridylmethyl)amine. Two cis‐sites, which are occupied by labile acetonitrile molecules in 1 and 2, are available for coordination of H2O2 and substituted benzoic acids. The hydroxylation of the aromatic ring occurs exclusively in the vicinity of the anchoring carboxylate functional group: ortho‐hydroxylation affords salicylates, whereas ipso‐hydroxylation with concomitant decarboxylation yields phenolates. The outcome of the substituent‐directed hydroxylation depends on the electronic properties and the position of substituents in the molecules of substrates: 3‐substituted benzoic acids are preferentially ortho‐hydroxylated, whereas 2‐ and, to a lesser extent, 4‐substituted substrates tend to undergo ipso‐hydroxylation/decarboxylation. These two pathways are not mutually exclusive and likely proceed via a common intermediate. Electron‐withdrawing substituents on the aromatic ring of the carboxylic acids disfavor hydroxylation, indicating an electrophilic nature for the active oxidant. Complexes 1 and 2 exhibit similar reactivity patterns, but 1 generates a more powerful oxidant than 2. Spectroscopic and labeling studies exclude acylperoxoiron(III) and FeIVO species as potential reaction intermediates, but strongly indicate the involvement of an FeIIIOOH intermediate that undergoes intramolecular acid‐promoted heterolytic OO bond cleavage, producing a transient iron(V) oxidant.
Metastable Aluminum(I) Compounds: Experimental and Quantum Chemical Investigations on Aluminum(I) Phosphanides—An Alternative Channel to the Disproportionation Reaction?
Authors: Henke Patrick , Schnöckel Hansgeorg 
Published: October 2009

AbstractThe well known thermodynamic instability of Al and Ga monohalides is caused by the favored disproportionation process to the bulk metal and the trihalides. During this highly complex process, a number of metalloid clusters that are intermediates on the way to the metal have been trapped. Therefore, all observations in the field of metalloid Al/Ga clusters have been traced to this favored disproportionation process. The failure to form phosphanide‐substituted Al clusters, in contrast to the generation of similar Ga clusters and analogous Al amide clusters, was the starting point of this contribution. For aluminum(I) phosphanides, there exists a different decomposition route in which the salt‐like bulk material AlP and not Al metal is the final product. The synthesis of two molecular “AlP” intermediate species, together with supporting DFT calculations, provide plausible arguments for this decomposition route, which is thermodynamically favored for many AlR/GaR species and which, surprisingly, has not been discussed before.
Dendritic Porphyrin–Fullerene Conjugates: Efficient Light‐Harvesting and Charge‐Transfer Events
Authors: Schlundt Sebastian , Kuzmanich Gregory , Spänig Fabian , de Miguel Rojas Gustavo , Kovacs Christian , Garcia‐Garibay Miguel A. , Guldi Dirk. M. , Hirsch Andreas 
Published: October 2009

AbstractA novel dendritic C60‐H2P‐(ZnP)3 (P=porphyrin) conjugate gives rise to the successful mimicry of the primary events in photosynthesis, that is, light harvesting, unidirectional energy transfer, charge transfer, and charge‐shift reactions. Owing, however, to the flexibility of the linkers that connect the C60, H2P, and ZnP units, the outcome depends strongly on the rigidity/viscosity of the environment. In an agar matrix or Triton X‐100, time‐resolved transient absorption spectroscopic analysis and fluorescence‐lifetime measurements confirm the following sequence. Initially, light harvesting is seen by the peripheral C60‐H2P‐ *(ZnP)3 conjugate. Once photoexcited, a unidirectional energy transfer funnels the singlet excited‐state energy to H2P to form C60‐*(H2P)‐(ZnP)3, which powers an intramolecular charge transfer that oxidizes the photoexcited H2P and reduces the adjacent C60 species. In the correspondingly formed (C60).−‐(H2P).+‐(ZnP)3 conjugate, an intramolecular charge‐shift reaction generates (C60).−‐H2P‐(ZnP)3.+, in which the radical cation resides on one of the three ZnP moieties, and for which lifetimes of up to 460 ns are found. On the other hand, investigations in organic media (i.e., toluene, THF, and benzonitrile) reveal a short cut, that is, the peripheral ZnP unit reacts directly with C60 to form (C60).−‐H2P‐(ZnP)3.+. Substantial configurational rearrangements— placing ZnP and C60 in proximity to each other—are, however, necessary to ensure the required through space interactions (i.e., close approach). Consequently, the lifetime of (C60).−‐H2P‐(ZnP)3.+ is as short as 100 ps in benzonitrile.
ChemInform Abstract: New Coumarin Diol (I) from the Plant Chloroxylon swietenia DC.
Authors: Rao G. Venkateswara , Rao K. Sambasiva , Annamalai T. , Mukhopadhyay T. 
Published: October 2009

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Recent Conceptual and Technological Advances in Polydiacetylene‐Based Supramolecular Chemosensors
Authors: Yoon Bora , Lee Sumi , Kim Jong‐Man 
Published: October 2009

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.