bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multi‐Component Synthesis of Dihydropyrimidines by Iodine Catalyst at Ambient Temperature and in‐vitro Antimycobacterial Activity
Authors: Zalavadiya Paresh , Tala Satish , Akbari Jignesh , Joshi Hitendra 
Published: June 2009

AbstractAn efficient and simple three‐component domino synthesis of some new dihydropyrimidines (DHPMs) from aromatic aldehydes, 1,3‐dicarbonyl compounds and N‐(3‐chloro‐4‐fluorophenyl)urea using molecular iodine as catalyst is described. The 1‐substituted dihydropyrimidines were isolated in good to excellent yields (78‐90%) within a short reaction time (4‐6 h) at ambient temperature. The biological evaluation revealed that the newly synthesized compounds (4a‐i and 5a‐i) exhibited moderate antimycobacterial activity against Mycobacterium tuberculosis H37 RV.
Synthesis and Cytotoxic Activity of Novel Amidine Analogues of Bis(2‐chloroethyl)amine
Authors: Bielawski Krzysztof , Bielawska Anna , Poplawska Bozena 
Published: June 2009

AbstractNovel nitrogen mustard agents 7–12 involving 4‐(N,N‐bis(2‐chloroethyl)aminophenyl)propylamine linked to a 5‐(4‐N‐alkylamidinophenyl)‐2‐furancarboxylic acid moiety by the formation of an amide bond have been synthesized, characterized, and evaluated for their in‐vitro cytotoxic activity against MDA‐MB‐231 and MCF‐7 human breast cancer cells. Evaluation of the cytotoxicity of 7–12 employing a MTT assay and inhibition of [3H]thymidine incorporation into DNA demonstrated that these compounds exhibit remarkable cytotoxic effects in comparison with 4‐[bis(2‐chloroethyl)amino]benzenebutanoic acid. Compounds 7 and 9, which possess a cationic amidine and 4,5‐dihydro‐1H‐imidazol function moiety are approximately ten times more potent than 4‐[bis(2‐chloroethyl)amino]benzenebutanoic acid. The new compounds were evaluated as DNA topoisomerase II inhibitors. The cytotoxicity of the compounds 7–12 correlates with their DNA‐binding affinities and their relative potency as topoisomerase II inhibitors.
Benzothiazole Incorporated Barbituric Acid Derivatives: Synthesis and Anticonvulsant Screening
Authors: Siddiqui Nadeem , Ahsan Waquar 
Published: June 2009

AbstractA series of 1‐(6‐substituted‐1,3‐benzothiazol‐2‐yl)‐3‐(substituted phenyl)hexahydro‐2,4,6‐pyrimidinetriones4a–twere synthesized starting from substituted anilines. These compounds contained two active anticonvulsant pharmacophores, benzothiazole and barbituric acid. Structures of the compounds were confirmed on the basis of different spectroscopic techniques. All the compounds were evaluated for their anticonvulsant activity. Three compounds4c,4d, and4sshowed promising anticonvulsant activities in Maximal Electroshock Seizure test (MES) and subcutaneous pentylenetetrazole test (scPTZ). They also displayed a wide safety profile when tested for the minimal motor impairment test.
Comparison of two methods of conducting the fit and strong! program
Authors: Seymour Rachel B. , Hughes Susan L. , Campbell Richard T. , Huber Gail M. , Desai Pankaja 
Published: June 2009

AbstractObjectiveFit and Strong! is an award winning, evidence‐based, multiple‐component physical activity/behavior change intervention. It is a group‐ and facility‐based program that meets for 90 minutes 3 times per week for 8 weeks (24 sessions total). We originally tested Fit and Strong! using physical therapists (PTs) as instructors but have transitioned to using nationally certified exercise instructors (CEIs) as part of an effort to translate Fit and Strong! into community‐based settings, and have tested the impact of this shift in instruction type on participant outcomes.MethodsWe used a 2‐group design. The first 161 participants to sequentially enroll received instruction from PTs. The next 190 sequential enrollees received instruction from CEIs. All participants were assessed at baseline, at the conclusion of the 8‐week Fit and Strong! program, and at the 6‐month followup.ResultsWe saw no significant differences by group on outcomes at 8 weeks or 6 months. Participants in both groups improved significantly with respect to lower‐extremity strength, aerobic capacity, pain, stiffness, and physical function. Significant differences favoring the PT‐led classes were seen on 2 of 5 mediators, self‐efficacy for exercise and barriers adherence efficacy. Participant evaluations rated both types of instruction equally highly, attendance was identical, and no untoward health events were observed or reported under either instruction mode.ConclusionOutcomes under the 2 types of instruction are remarkably stable. These findings justify the use of CEIs in the future to extend the reach of the Fit and Strong! program.
Gene expression signatures in polyarticular juvenile idiopathic arthritis demonstrate disease heterogeneity and offer a molecular classification of disease subsets
Authors: Griffin Thomas A. , Barnes Michael G. , Ilowite Norman T. , Olson Judyann C. , Sherry David D. , Gottlieb Beth S. , Aronow Bruce J. , Pavlidis Paul , Hinze Claas H. , Thornton Sherry , Thompson Susan D. , Grom Alexei A. , Colbert Robert A. , Glass David N. 
Published: June 2009

AbstractObjectiveTo determine whether peripheral blood mononuclear cells (PBMCs) from children with recent‐onset polyarticular juvenile idiopathic arthritis (JIA) exhibit biologically or clinically informative gene expression signatures.MethodsPeripheral blood samples were obtained from 59 healthy children and 61 children with polyarticular JIA prior to treatment with second‐line medications, such as methotrexate or biologic agents. RNA was extracted from isolated mononuclear cells, fluorescence labeled, and hybridized to commercial gene expression microarrays (Affymetrix HG‐U133 Plus 2.0). Data were analyzed using analysis of variance at a 5% false discovery rate threshold after robust multichip analysis preprocessing and distance‐weighted discrimination normalization.ResultsInitial analysis revealed 873 probe sets for genes that were differentially expressed between polyarticular JIA patients and healthy controls. Hierarchical clustering of these probe sets distinguished 3 subgroups within the polyarticular JIA group. Prototypical patients within each subgroup were identified and used to define subgroup‐specific gene expression signatures. One of these signatures was associated with monocyte markers, another with transforming growth factor β–inducible genes, and a third with immediate early genes. Correlation of gene expression signatures with clinical and biologic features of JIA subgroups suggested relevance to aspects of disease activity and supported the division of polyarticular JIA into distinct subsets.ConclusionGene expression signatures in PBMCs from patients with recent‐onset polyarticular JIA reflect discrete disease processes and offer a molecular classification of disease.
Anti‐DNA antibody induction of protein kinase C phosphorylation and fibronectin synthesis in human and murine lupus and the effect of mycophenolic acid
Authors: Yung Susan , Zhang Qing , Zhang Chen Zhu , Chan Kwok Wah , Lui Sing Leung , Chan Tak Mao 
Published: June 2009

AbstractObjectiveTo examine fibronectin (FN) expression in human lupus nephritis and the effect of anti‐DNA antibodies on transforming growth factor β1 (TGFβ1) and FN synthesis in cultured human mesangial cells. The effects of mycophenolic acid (MPA) on this pathway, and the effects of mycophenolate mofetil (MMF) treatment in (NZB × NZW)F1/J mice were also studied.MethodsImmunohistochemical analyses of renal biopsy samples from patients with active diffuse proliferative lupus nephritis were performed. Cultured human mesangial cells were incubated with human polyclonal anti‐DNA antibodies, with or without MPA. (NZB × NZW)F1/J mice with active nephritis were randomized to receive either MMF (100 mg/kg/day) or vehicle treatment for 12 weeks.ResultsGlomerular FN expression was increased in patients with lupus nephritis, and it colocalized with IgG deposition. Anti‐DNA antibodies induced protein kinase Cα (PKCα), PKCβI, and PKCβII activation, increased levels of bioactive TGFβ1, and increased FN synthesis in human mesangial cells (P < 0.001 for each comparison versus control conditions). Pretreatment of anti‐DNA antibodies with exogenous DNA reduced their cellular binding and abrogated their induction of TGFβ1 and FN synthesis. Inhibition of PKC activation in human mesangial cells prior to anti‐DNA antibody stimulation had no effect on cell proliferation, but resulted in significantly reduced antibody‐mediated TGFβ1 secretion and FN synthesis. MPA treatment down‐regulated PKCα, PKCβI, and PKCβII phosphorylation, reduced levels of TGFβ1 bioactivation, and decreased FN synthesis and deposition into the extracellular matrix. MMF treatment in (NZB × NZW)F1/J mice resulted in a reduction in glomerular IgG deposition, PKC activation, and FN expression, as well as an amelioration of proteinuria.ConclusionHuman polyclonal anti‐DNA antibodies induce TGFβ1 and FN synthesis in human mesangial cells through PKC activation, which is inhibited by MPA.
Clinical and immunogenetic prognostic factors for radiographic severity in ankylosing spondylitis
Authors: Ward Michael M. , Hendrey Matthew R. , Malley James D. , Learch Thomas J. , Davis John C. , Reveille John D. , Weisman Michael H. 
Published: June 2009

AbstractObjectiveTo improve prognostic ability in ankylosing spondylitis (AS), we sought to identify demographic, clinical, and immunogenetic characteristics associated with radiographic severity in a large cohort of patients.MethodsPatients with AS for ≥20 years were enrolled in a cross‐sectional study (n = 398). Pelvic and spinal radiographs were scored using the Bath Ankylosing Spondylitis Radiology Index for the spine (BASRI‐s), and radiographic severity was measured as the BASRI‐s/duration of AS. Clinical factors and HLA–B, DR, DQ, and DP alleles associated with the highest quartile of the distribution of radiographic severity were identified by first using random forests and then using multivariable logistic regression modeling. Similar procedures were used to identify factors associated with the lowest quartile of radiographic severity.ResultsRadiographic severity (being in the top quartile of BASRI‐s/duration of AS) was associated with older age at onset of AS (odds ratio [OR] 1.10 per year), male sex (OR 1.90), current smoker (OR 4.72), and the presence of HLA–B*4100 (OR 11.73), DRB1*0804 (OR 12.32), DQA1*0401 (OR 5.24), DQB1*0603 (OR 3.42), and DPB1*0202 (OR 23.36), whereas the presence of DRB1*0801 was strongly negatively associated (OR 0.03). Being in the lowest quartile of BASRI‐s/duration of AS was also less likely among those with an older age at onset of AS (OR 0.94 per year), men (OR 0.28), and current smokers (OR 0.29).ConclusionThe accuracy of the prognosis of radiographic severity in AS is improved by knowing the age at disease onset, sex, smoking history, and the presence of HLA–B*4100, DRB1*0804, DQA1*0401, DQB1*0603, DRB1*0801, and DPB1*0202 alleles.
Anti–U11/U12 RNP antibodies in systemic sclerosis: A new serologic marker associated with pulmonary fibrosis
Authors: Fertig Noreen , Domsic Robyn T. , Rodriguez‐Reyna Tatiana , Kuwana Masataka , Lucas Mary , Medsger Thomas A. , Feghali‐Bostwick Carol A. 
Published: June 2009

AbstractObjectiveTo characterize a new serum autoantibody in patients with systemic sclerosis (SSc) directed against U11/U12 RNP and to identify the clinical features associated with this autoantibody.MethodsWe identified autoantibodies directed against the U11/U12 RNP complex in sera of patients with SSc and confirmed antibody specificity by immunoprecipitation, reverse transcriptase–polymerase chain reaction, and Southern blotting. We determined the prevalence of these antibodies in SSc and their specificity for SSc. We compared anti–U11/U12 RNP autoantibody–positive and negative SSc patients on demographic, disease classification, clinical variables, and survival.ResultsWe identified 33 patients with anti–U11/U12 RNP antibodies. In 2 consecutive series of SSc patients first seen at 10‐year intervals (1994–1995 and 2004–2005), the prevalence of anti–U11/U12 RNP antibody–positive patients was 15 of 462 (3.2%). Seventeen (52%) of these 33 patients had limited cutaneous involvement. All patients had Raynaud's phenomenon and 82% had gastrointestinal (GI) involvement. None had “intrinsic” pulmonary arterial hypertension. The most significant clinical difference between anti–U11/U12 antibody–positive and negative cohorts was the prevalence of lung fibrosis, which occurred in 79% of the anti–U11/U12 RNP antibody–positive patients versus 37% of the anti–U11/U12 RNP antibody–negative patients (P < 0.0001). GI involvement was also significantly increased in the anti–U11/U12 RNP antibody–positive group. Patients with anti–U11/U12 RNP antibodies and pulmonary fibrosis had a 2.25‐fold greater risk of death than anti–U11/U12 RNP negative patients with pulmonary fibrosis.ConclusionAnti–U11/U12 RNP antibodies are present in the sera of approximately 3% of patients with SSc and are a marker for lung fibrosis, which is often severe.
Disease remission state in patients treated with the combination of tumor necrosis factor blockade and methotrexate or with disease‐modifying antirheumatic drugs: A clinical and imaging comparative study
Authors: Saleem Benazir , Brown Andrew K. , Keen Helen , Nizam Sharmin , Freeston Jane , Karim Zunaid , Quinn Mark , Wakefield Richard , Hensor Elizabeth , Conaghan Philip G. , Emery Paul 
Published: June 2009

AbstractObjectiveFor patients with rheumatoid arthritis (RA) in remission who are receiving disease‐modifying antirheumatic drugs (DMARDs), radiographic progression correlates with imaging‐detected synovitis as measured by power Doppler activity. In contrast, patients with disease in remission who are receiving the combination of tumor necrosis factor (TNF) blockade with methotrexate (MTX) (combination treatment) have reduced radiographic damage for the equivalent clinical state. We undertook this study to determine whether the difference in radiographic outcome is a result of more complete suppression of imaging‐detected synovitis.MethodsOne hundred patients with RA in remission (Disease Activity Score in 28 joints [DAS28] <2.6) for at least 6 months while receiving either combination treatment (n = 50) or DMARDs (n = 50) were matched for clinical variables. Ultrasound of metacarpophalangeal joints 1–5 and the wrist joints was performed. Remission according to imaging results was defined as a score of 0 for both grey scale synovitis and power Doppler activity.ResultsIn patients receiving combination treatment or DMARDs (median DAS28 1.65 versus 1.78, median disease duration 120 months versus 90 months, and median duration of remission 13 months versus 18 months), the proportion with remission according to imaging results was not significantly different (10% versus 16%, respectively). The combination treatment group had more grey scale synovitis (P < 0.001) but similar power Doppler activity (48% versus 60%, respectively; P = 0.229) in any joint as compared with the DMARD group. Results were not affected by stratification for duration of disease or remission.ConclusionIn RA patients with disease in remission, imaging‐detected synovitis persists, with power Doppler activity seen in ≥48% of the patients regardless of therapy. These results suggest that superior radiographic outcomes in patients treated with the combination of TNF blockade and MTX may not be due to complete suppression of imaging‐detected synovitis.
Spondylarthritis in HLA–B27/human β2‐microglobulin–transgenic rats is not prevented by lack of CD8
Authors: Taurog Joel D. , Dorris Martha L. , Satumtira Nimman , Tran Tri M. , Sharma Rohit , Dressel Ralf , van den Brandt Jens , Reichardt Holger M. 
Published: June 2009

AbstractObjectiveHLA–B27 predisposes to spondylarthritis by an unknown mechanism. A logical candidate mechanism is through recognition of B27 by CD8+ T cells. The purpose of this study was to examine the effects of a lack of CD8 on the spondylarthritis that develops in B27/human β2‐microglobulin (Huβ2m)–transgenic rats.MethodsA missense mutation in the CD8a gene that causes a loss of CD8α expression was identified in offspring of a male Sprague‐Dawley rat that had been treated with the mutagen N‐ethyl‐N‐nitrosourea. The mutation was crossed into B27/Huβ2m‐transgenic lines on the Lewis background. CD8a–/– and CD8a+/– progeny were compared on a mixed SD‐LEW background as well as after at least 10 backcrosses to LEW rats. CD8 function was assessed by generating cytolytic T lymphocytes (CTLs) against allogeneic DA strain antigens.ResultsHomozygous mutant rats showed normal CD8a and CD8b messenger RNA levels but no detectable expression of either protein and an almost complete abrogation of the allogeneic CTL response. Two disease phenotypes previously observed in different B27/Huβ2m‐transgenic lines also occurred in the respective CD8a–/–‐transgenic rat lines. There was no significant difference in disease prevalence or severity between CD8a–/– rats and CD8a+/– rats.ConclusionAll of the previously described disease manifestations in HLA–B27/Huβ2m‐transgenic rats arise in the absence of any functional CD8+ T cells. It thus seems unlikely that classic T cell recognition of HLA–B27 is of primary importance in this animal model. The possibility of a secondary role of a CD8‐dependent mechanism cannot be entirely excluded.
Induction of CCL13 expression in synovial fibroblasts highlights a significant role of oncostatin M in rheumatoid arthritis
Authors: Hintzen Christoph , Quaiser Saskia , Pap Thomas , Heinrich Peter C. , Hermanns Heike M. 
Published: June 2009

AbstractObjectiveTo investigate the molecular mechanisms of CCL13/monocyte chemoattractant protein 4 (MCP‐4) chemokine expression through proinflammatory cytokines in different primary human fibroblasts and the contribution of CCL13 to monocyte migration.MethodsUsing RNase protection assays and enzyme‐linked immunosorbent assays, we quantified the expression of CCL13 compared with that of CCL2/MCP‐1 in primary human fibroblasts. Boyden chamber assays were performed to determine the importance of CCL13 for migration of primary monocytes. Pharmacologic inhibitors as well as small interfering RNA knockdown approaches were used to investigate the signaling pathways regulating CCL13 expression.ResultsThe interleukin‐6 (IL‐6)–type cytokine oncostatin M (OSM) was a powerful inducer of CCL13 expression in primary synovial fibroblasts from patients with rheumatoid arthritis (RA) as well as those from healthy control subjects but not in other types of fibroblasts. Neither IL‐6 nor tumor necrosis factor α could stimulate the expression of CCL13 in synovial fibroblasts; IL‐1β was a very weak inducer. Synovial fibroblasts from patients with RA constitutively produced low amounts of CCL13, which was partially dependent on constitutive production of OSM. By investigating the underlying molecular mechanism, we identified STAT‐5, ERK‐1/2, and p38 as critical factors involved in OSM‐dependent transcription and messenger RNA stabilization of CCL13.ConclusionIn contrast to other prominent cytokines involved in the pathogenesis of RA, OSM can strongly up‐regulate the expression of CCL13, a chemokine recently identified in the synovial fluid of patients with RA. Despite potent OSM‐induced signal transduction in all types of fibroblasts analyzed, only synovial fibroblasts secreted CCL13, which might be indicative of tissue‐specific imprinting of different fibroblasts during development.
Development of a structured interview tool to help patients identify and solve rheumatic condition‐related work barriers
Authors: Allaire Saralynn , Keysor Julie J. 
Published: June 2009

AbstractObjectiveTo develop a comprehensive and efficient assessment tool for rheumatic condition‐related work barriers and explore its use by physical and occupational therapists.MethodsLiterature on arthritis work barriers was examined, followed by the collection of qualitative data on work barriers from patients with rheumatic conditions. A tool called the Work Experience Survey‐Rheumatic Conditions (WES‐RC), which identifies barriers and facilitates the formation of solutions for barriers, was developed using this data. Ten physical and occupational therapists reviewed the initial version of the tool and provided qualitative data and the relevance of its use by therapists. Using this data, the WES‐RC was revised. The therapists then administered the WES‐RC to 20 patients. Quantitative data, qualitative data, and results of the administrative experience were collected from therapists after each administration. Relevant data were used to further revise the WES‐RC. Qualitative data were coded and themes developed by 2 readers and compared. Means and frequencies were used to describe the quantitative data.ResultsThe WES‐RC addressed patients' work barriers quite well with a mean score of 8.7, on a scale of 1–10 where 10 = barriers completely covered, and administration time was reported as “about right” in 18 (90%) of 20 administrations. Eighty percent of the therapists' administration experiences were positive. Therapists reported barrier identification as easy, while solution formation was difficult in 45% of the administrations and judged insufficient in 35%.ConclusionThe WES‐RC appears to be feasible for rheumatology patients and for use by physical and occupational therapists. Further study is needed to enhance effective solution formation.
Being careful: A grounded theory of emergent chronic knee problems
Authors: Maly Monica R. , Cott Cheryl A. 
Published: June 2009

AbstractObjectiveTo gain insight into the prediagnostic stages of knee osteoarthritis (OA) and identify the process whereby people recognize and address emergent chronic knee problems.MethodsTwenty‐six people (15 women, mean age 53.2 ± 7.4 years) participated in a grounded theory study. Ten participants had a recent diagnosis of knee OA, and 16 had no diagnosis. The undiagnosed participants self‐reported their symptoms, which had lasted at least 6 months and were consistent with knee OA. During semistructured, one‐on‐one interviews, participants reflected on the development and impact of their chronic knee problems. A constant comparative approach was used for analysis.ResultsParticipants described uncertainty in understanding the meaning of intermittent knee symptoms for several years before becoming aware of the emergence of chronic knee problems. Once aware, participants engaged in a circular process of interpreting the meaning of knee symptoms and being careful. Being careful referred to the cycle of perceptions, intentions, and behaviors aimed at avoiding knee damage during physical activity. This cycle continued until participants experienced a disruption that challenged their participation in meaningful activities, at which time they decided to access health care.ConclusionAs a new construct, being careful unifies the complex set of experiences and behaviors that describe how participants protected their knee during physical activity. Participants interpret the experiences associated with emerging knee problems through interactions with others. These interactions enhance the participants' self‐management, despite not having the benefits associated with diagnosis, such as justification for symptoms and formal assistance.