bluuebunny/crossref_metadata_2025_split huggingface dataset:
Generation of Multiple Fluid-Phase C3b:Plasma Protein Complexes during Complement Activation: Possible Implications in C3 Glomerulopathies
Authors: Ramadass Mahalakshmi , Ghebrehiwet Berhane , Smith Richard J. , Kew Richard R. 
Published: December 2013

Abstract
The complement system is tightly regulated to safeguard against tissue damage that results from unwanted activation. The key step of C3 cleavage to C3b is regulated by multiple mechanisms that control the initiation and extent of activation. This study demonstrated that C3b:plasma protein complexes form in the fluid-phase during complement activation. Several different plasma proteins displayed a discrete high molecular SDS-resistant band when any of the three complement activating pathways were triggered in normal human serum or plasma. Serum depleted of individual complement proteins revealed that C3 and factors B and D were essential for complex formation. Inactivation of the thioester bond in C3 also prevented complex formation. In vitro, complexes could be generated using four purified proteins—C3, factor B, factor D, and target protein—and Mg2+ to allow C3 convertase formation. These studies showed that the complexes consisted of a plasma protein covalently bound to C3b in a 1:1 molar ratio; the C3b portion was rapidly degraded by factors H and I. Analysis of plasma samples from patients with dense deposit disease and C3 glomerulonephritis demonstrated that C3b:protein complexes form spontaneously in the blood of patients with dense deposit disease and, to a lesser extent, in C3 glomerulonephritis patients, but not in healthy controls. This finding supports the underlying hypothesis that these C3 glomerulopathies are diseases of fluid-phase complement dysregulation. These complexes could normally function as a passive mechanism to intercept C3b from depositing on host cells. However, excessive generation and/or defective clearance of fluid-phase C3b:protein complexes may have pathological consequences.
Variations Among Primary Care Physicians in Exercise Advice, Imaging, and Analgesics for Musculoskeletal Pain: Results From a Factorial Experiment
Authors: Maserejian Nancy N. , Fischer Michael A. , Trachtenberg Felicia L. , Yu Jing , Marceau Lisa D. , McKinlay John B. , Katz Jeffrey N. 
Published: December 2013

ObjectiveTo examine whether medical decisions regarding evaluation and management of musculoskeletal pain conditions varied systematically by characteristics of the patient or provider.MethodsWe conducted a balanced factorial experiment among primary care physicians in the US. Physicians (n = 192) viewed 2 videos of different patients (actors) presenting with pain: undiagnosed sciatica symptoms or diagnosed knee osteoarthritis. Systematic variations in patient gender, socioeconomic status, and race and physician gender and experience (<20 versus ≥20 years in practice) permitted estimation of unconfounded effects. Analysis of variance was used to evaluate associations between patient or provider attributes and clinical decisions. Quality of decisions was defined based on the current recommendations of the American College of Rheumatology, American Pain Society, and clinical expert consensus.ResultsDespite current recommendations, less than one‐third of physicians would provide exercise advice (30.2% for osteoarthritis and 32.8% for sciatica). Physicians with fewer years in practice were more likely to provide advice on lifestyle changes, particularly exercise (P ≤ 0.01), and to prescribe nonsteroidal antiinflammatory drugs for pain relief, both of which were appropriate and consistent with current recommendations for care. Newer physicians ordered fewer tests, particularly basic laboratory investigations or urinalysis. Test ordering decreased as organizational emphasis on business or profits increased. Patient factors and physician gender had no consistent effects on pain evaluation or treatment.ConclusionPhysician education on disease management recommendations regarding exercise and analgesics and implementation of quality measures may be useful, particularly for physicians with more years in practice.
Is Patellofemoral Osteoarthritis Common in Middle‐Aged People With Chronic Patellofemoral Pain?
Authors: Hinman Rana S. , Lentzos Jonathan , Vicenzino Bill , Crossley Kay M. 
Published: December 2013

ObjectiveTo document the prevalence of radiographic osteoarthritis (OA) in the medial and lateral patellofemoral (PF) joint compartments relative to the prevalence of tibiofemoral (TF) joint OA in middle‐aged and older adults with chronic PF knee pain.MethodsA convenience sample of 224 people who volunteered for a clinical trial underwent weight‐bearing posteroanterior and skyline knee radiographs of their most symptomatic eligible knee. Radiographic severity in the TF joint and in the medial and lateral PF joint compartments was independently graded by 2 examiners using the Kellgren/Lawrence (K/L) grading system. K/L grades ≥2 were considered evidence of OA.ResultsOA was common in this cohort, and the most prevalent pattern was combined TF joint and PF joint OA (n = 98 [44%]), followed by isolated PF joint OA (n = 57 [25%]). Isolated TF joint OA was rare. Overall, more people demonstrated radiographic OA in the PF joint (n = 155 [69%]) than in the TF joint (n = 100 [45%]). The majority of people with PF joint OA had OA in both the medial and lateral PF joint compartments (n = 98 [63%]). Even in people ages <50 years, radiographic OA was common (isolated PF joint OA, 26% [n = 21]; combined TF joint and PF joint OA, 29% [n = 23]). The severity of PF joint OA was similar across men and women.ConclusionPF joint OA was highly prevalent, more so than TF joint OA, and even in individuals ages <50 years. Further research is needed to elucidate the cause and effect relationship between chronic PF pain and PF joint OA.
Evaluating Appropriate Use of Prophylactic Colchicine for Gout Flare Prevention
Authors: George Michael , Pullman‐Mooar Sally , Hussain Fauzia , Schumacher H. Ralph 
Published: December 2013

ObjectiveAmerican College of Rheumatology and European League Against Rheumatism guidelines recommend colchicine to prevent gout flares in patients initiating and increasing uric acid–lowering therapy until serum uric acid is maintained at ≤6 mg/dl. We aimed to evaluate how well colchicine prescribing practices adhere to these guidelines and to examine factors associated with improved prescribing.MethodsElectronic medical records were reviewed for 126 patients with active colchicine prescriptions for prophylaxis of gout flares. Colchicine prescribing was defined as inappropriate if 1) no concurrent urate‐lowering therapy was prescribed, 2) uric acid was not at goal and urate‐lowering therapy had not been increased in the past 3 months, or 3) uric acid goals were met for >1 year and flares had resolved in the absence of tophi.ResultsColchicine use was considered inappropriate in 93 patients (73.8%). Thirty‐four were prescribed no urate‐lowering therapy, 50 were above the uric acid goal without urate‐lowering therapy increase in the prior 3 months, and 9 were at the uric acid goal for >1 year without flares or tophi. Patients appropriately prescribed colchicine were younger and were more likely to have been seen by a rheumatologist. Allopurinol dose and allergy, uric acid level, and renal function were similar in the 2 groups.ConclusionWe found a high prevalence of what we considered inappropriate prophylactic colchicine use, driven largely by failure to prescribe concurrent urate‐lowering therapies or adequately increase these medications. Rheumatology consultation was associated with improved colchicine prescribing.
Retrospective cohort study of a microelectronics and business machine facility
Authors: Silver Sharon R. , Pinkerton Lynne E. , Fleming Donald A. , Jones James H. , Allee Steven , Luo Lian , Bertke Stephen J. 
Published: December 2013

AbstractObjectivesWe examined health outcomes among 34,494 workers employed at a microelectronics and business machine facility 1969–2001.MethodsStandardized mortality ratio (SMR) and standardized incidence ratios were used to evaluate health outcomes in the cohort and Cox regression modeling to evaluate relations between scores for occupational exposures and outcomes of a priori interest.ResultsJust over 17% of the cohort (5,966 people) had died through 2009. All cause, all cancer, and many cause‐specific SMRs showed statistically significant deficits. In hourly males, SMRs were significantly elevated for non‐Hodgkin's lymphoma and rectal cancer. Salaried males had excess testicular cancer incidence. Pleural cancer and mesothelioma excesses were observed in workers hired before 1969, but no available records substantiate use of asbestos in manufacturing processes. A positive, statistically significant relation was observed between exposure scores for tetrachloroethylene and nervous system diseases.ConclusionsFew significant exposure–outcome relations were observed, but risks from occupational exposures cannot be ruled out due to data limitations and the relative youth of the cohort. Am. J. Ind. Med. 57:412–424, 2014. © 2013 Wiley Periodicals, Inc.
Flame‐retardant properties of acrylonitrile–butadiene–styrene/wood flour composites filled with expandable graphite and ammonium polyphosphate
Authors: Zheng Jianqiang , Li Bin , Guo Chuigen , Wu Qiong , Wang Yufeng 
Published: December 2013

ABSTRACTExpandable graphite (EG) and ammonium polyphosphate (APP) were used to improve the flame retardancy of acrylonitrile–butadiene–styrene based wood–plastic composites (WPCs). A synergistic effect between EG and APP on the flame retardancy of the WPCs was proposed. The results show that the highest limited oxygen index (LOI) of 34.2% and a V‐0 rating were achieved when the ratio of EG to APP 12.5:7.5; this comprised 20 wt % of the total amount. However, LOI values of the samples with EG and APP alone were only 30.5 and 24.5%, respectively. Thermogravimetric analysis indicated that the flame retardants improved the amount of residue. The EG and EG/APP additives greatly decreased the peak heat release rate and suppressed smoke according to cone calorimetry testing. The scanning electron microscopy analysis indicated that the surface of the wormlike char was covered with a granular substance, which may have been the viscous phosphoric acid or poly(phosphoric acid) decomposed from APP. The flame‐retardant additives worsened the mechanical properties of the WPCs. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40281.
Photoresponsive nanogels synthesized using spiropyrane‐modified pullulan as potential drug carriers
Authors: Wang Bin , Chen Kefu , Yang Ren‐dang , Yang Fei , Liu Jin 
Published: December 2013

AbstractReversible light‐responsive nanogels were constructed from an amphiphilic spiropyrane‐modified pullulan (SpP). The polymer was synthesized by modifying a biodegradable pullulan with carboxyl‐containing spiropyrane (Sp) molecules. The SpP structure was confirmed by the appearance of a carbonyl signal in the FT‐IR and 1H NMR spectra. The nanogels can be controlled by photostimulation, which results in the reversible structural transformation of the hydrophobic Sp to the hydrophilic merocyanine. The physical properties of the nanogels were confirmed to change dramatically after being irradiated with different wavelengths of light. Drug delivery tests showed that the model drug pyrene was completely captured by the nanogels and then released from the SpP nanogels in a light‐dependent manner. This study provides an alternative approach to constructing light‐responsive nanocarriers with excellent biocompatibility for drug uptake and release. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40288.
Enhanced atomic oxygen erosion resistance and mechanical properties of graphene/cellulose acetate composite films
Authors: Liu Lei , Shen Zhigang , Liang Shuaishuai , Yi Min , Zhang Xiaojing , Ma Shulin 
Published: December 2013

ABSTRACTThe application of graphene (Gr) to enhance atomic oxygen (AO) erosion resistance and mechanical properties was demonstrated in this study. Gr‐reinforced cellulose acetate (CA) composite films were obtained by flattening with a glass rod, and the AO erosion resistance was investigated in a plasma‐type, ground‐based AO effect simulation facility. Significant improvements in the mechanical properties and AO erosion resistance were achieved at relatively low Gr contents. A 59 ± 7% decrease in the mass loss and a 12 ± 3% increase in the tensile strength were achieved by the addition of only 1 wt % Gr. Moreover, the layered structure of the fractured surfaces and the excellent mechanical properties illustrated the homogeneous dispersion of Gr in the CA matrix and the strong interactions between Gr and CA. Furthermore, Gr flakes served as shields to defend the underside of CA from AO erosion because of the specific two‐dimensional structure and outstanding AO erosion resistance. Therefore, this research provides a new and effective strategy for improving the mechanical strength and AO erosion resistance of polymer materials. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40292.
Polar polystyrene‐isoprene‐styrene copolymers with long polybutadiene branches
Authors: Zhao Zhongfu , Wang Zhanyue , Zhang Chunqing , Wang Yongzhao , Li Zhansheng , Hu Yanming , Xiao Xuesong 
Published: December 2013

ABSTRACTPolar polystyrene‐isoprene‐styrene (SIS) copolymers having epoxide groups and long polybutadiene (PB) branches were synthesized via the combination of in situ epoxidation, anionic polymerization and graft‐onto reaction. They were characterized with 1H NMR, GPC, FT‐IR, DSC, and contact angle test. Their polarity was determined by the epoxidation degree and graft efficiency. The epoxidation degree linearly increased with the epoxidation time. The graft efficiency decreased with the branch length, but increased with the epoxidation degrees. Although their glass transition temperature (Tg) of diene blocks and flexibility properties had been negatively affected by in situ epoxidation, they could be modulated by the epoxidation degree, branch length, and branch density. Their Tg could be tailored by the branch length and branch density since they fitted the Fox equation very well, especially as the longer branches were grafted. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40303.
Gene Expression Pattern of Cells From Inflamed and Normal Areas of Osteoarthritis Synovial Membrane
Authors: Lambert Cécile , Dubuc Jean‐Emile , Montell Eulàlia , Vergés Josep , Munaut Carine , Noël Agnès , Henrotin Yves 
Published: December 2013

ObjectiveTo compare the gene expression patterns of synovial cells from inflamed or normal/reactive areas of synovial membrane obtained from the same patient with osteoarthritis (OA).MethodsAt the time of total knee replacement, synovial tissues were obtained from 12 patients with knee OA. The inflammation status of the synovial membrane was characterized according to macroscopic criteria and classified as normal/reactive or inflamed. Biopsy samples were cultured separately for 7 days. Microarray gene expression profiling was performed on normal/reactive and inflamed areas. Western blot and immunohistochemistry were used to confirm the identified genes that were differentially expressed.ResultsWe identified 896 genes that were differentially expressed between normal/reactive and inflamed areas. The key pathways were related to inflammation, cartilage metabolism, Wnt signaling, and angiogenesis. In the inflammation network, the genes TREM1 and S100A9 were strongly up‐regulated. The genes MMP3, MMP9, CTSH (cathepsin H), and CTSS (cathepsin S) were significantly up‐regulated in the cartilage catabolism pathway, while the most up‐regulated anabolism enzyme gene was HAS1. In the Wnt signaling pathway, the genes for Wnt‐5a and low‐density lipoprotein receptor–related protein 5 were up‐regulated, while the gene FZD2 and the gene for Dkk‐3 were down‐regulated. Finally, STC1, which codes for a protein involved in angiogenesis, was identified as the most up‐regulated gene in inflamed compared with normal/reactive areas.ConclusionThis study is the first to identify different expression patterns between 2 areas of the synovial membrane from the same patient. These differences concern several key pathways involved in OA pathogenesis. This analysis also provides information regarding new genes and proteins as potential targets of treatment.
Alternative p38 MAPKs Are Essential for Collagen‐Induced Arthritis
Authors: Criado Gabriel , Risco Ana , Alsina‐Beauchamp Dayanira , Pérez‐Lorenzo María J. , Escós Alejandra , Cuenda Ana 
Published: December 2013

ObjectiveThe role of most p38 MAPK isoforms in inflammatory arthritis is not known. This study was undertaken to evaluate p38γ and p38δ deficiency in the collagen‐induced arthritis (CIA) model.MethodsWild‐type, p38γ−/−, p38δ−/−, and p38γ/δ−/− mice were immunized with chicken type II collagen, and disease activity was evaluated by semiquantitative scoring and histologic assessment. Serum cytokine levels and in vitro T cell cytokine responses were quantified by flow cytometry and multiplex analysis, and serum anticollagen antibody levels by enzyme‐linked immunosorbent assay. Cytokine and p38 MAPK isoform expression in joints were determined by quantitative polymerase chain reaction.ResultsCompound p38γ and p38δ deficiency markedly reduced arthritis severity compared with that in wild‐type mice, whereas lack of either p38γ or p38δ had an intermediate effect. Joint damage was minimal in arthritic p38γ/δ−/− mice compared with wild‐type mice. The p38γ/δ−/− mice had lower levels of pathogenic anticollagen antibodies and interleukin‐1β (IL‐1β) and tumor necrosis factor α than controls. In vitro T cell assays showed reduced proliferation, interferon‐γ (IFNγ) production, and IL‐17 production by lymph node cells from p38γ/δ−/− mice. IL‐17 and IFNγ messenger RNA expression in joints was significantly inhibited in p38γ/δ−/− mice. Wild‐type chimeric mice with p38γ/δ−/− bone marrow did not show decreased CIA.ConclusionReduced disease severity in p38γ/δ−/− mice was associated with lower cytokine production and anticollagen antibody responses than in controls, indicating that p38γ and p38δ are crucial regulators of inflammatory joint destruction in CIA. Our findings indicate that p38γ and p38δ are potential therapeutic targets in complex diseases, such as rheumatoid arthritis, that involve innate and adaptive immune responses.
Activation of Spinal NF‐κB/p65 Contributes to Peripheral Inflammation and Hyperalgesia in Rat Adjuvant‐Induced Arthritis
Authors: Luo Jian‐Gang , Zhao Xu‐Li , Xu Wei‐Cheng , Zhao Xue‐Jun , Wang Jun‐Nan , Lin Xiao‐Wen , Sun Tao , Fu Zhi‐Jian 
Published: December 2013

ObjectiveIt is known that noxious stimuli from inflamed tissue may increase the excitability of spinal dorsal horn neurons (a process known as central sensitization), which can signal back and contribute to peripheral inflammation. However, the underlying mechanisms have yet to be fully defined. A number of recent studies have indicated that spinal NF‐κB/p65 is involved in central sensitization, as well as pain‐related behavior. Thus, the aim of this study was to determine whether NF‐κB/p65 can facilitate a peripheral inflammatory response in rat adjuvant‐induced arthritis (AIA).MethodsLentiviral vectors encoding short hairpin RNAs that target NF‐κB/p65 (LV‐shNF‐κB/p65) were constructed for gene silencing. The spines of rats with AIA were injected with LV‐shNF‐κB/p65 on day 3 or day 10 after treatment with Freund's complete adjuvant (CFA). During an observation period of 20 days, pain‐related behavior, paw swelling, and joint histopathologic changes were evaluated. Moreover, the expression levels of spinal tumor necrosis factor α (TNFα), interleukin‐1β (IL‐1β), and cyclooxygenase 2 (COX‐2) were assessed on day 14 after CFA treatment.ResultsThe presence of peripheral inflammation in rats with AIA induced an increase in NF‐κB/p65 expression in the spinal cord, mainly in the dorsal horn neurons and astrocytes. Delivery of LV‐shNF‐κB/p65 to the spinal cord knocked down the expression of NF‐κB/p65 and significantly attenuated hyperalgesia, paw edema, and joint destruction. In addition, spinal delivery of LV‐shNF‐κB/p65 reduced the overexpression of spinal TNFα, IL‐1β, and COX‐2.ConclusionThese findings indicate that spinal NF‐κB/p65 plays an important role in the initiation and development of both peripheral inflammation and hyperalgesia. Thus, inhibition of spinal NF‐κB/p65 expression may provide a potential treatment to manage painful inflammatory disorders.
Suppression of Rheumatoid Arthritis B Cells by XmAb5871, an Anti‐CD19 Antibody That Coengages B Cell Antigen Receptor Complex and Fcγ Receptor IIb Inhibitory Receptor
Authors: Chu Seung Y. , Yeter Karen , Kotha Roshan , Pong Erik , Miranda Yvonne , Phung Sheryl , Chen Hsing , Lee Sung‐Hyung , Leung Irene , Bonzon Christine , Desjarlais John R. , Stohl William , Szymkowski David E. 
Published: December 2013

ObjectiveEngagement of Fcγ receptor IIb (FcγRIIb) suppresses B cell activation and represents a promising target for therapy in autoimmunity. The aim of this study was to characterize B cell immunosuppression mediated by the Fc‐engineered antibody, XmAb5871, which coengages FcγRIIb with the B cell antigen receptor (BCR) complex and that is currently in clinical development for the treatment of rheumatoid arthritis (RA). Because rheumatoid factor (RF) might interfere with the binding of XmAb5871 to FcγRIIb, we correlated RF titers with the potency of XmAb5871.MethodsWe analyzed the expression of CD19, FcγRIIb, and CD86 on naive and memory B cells from 50 patients with RA and 66 healthy donors, quantified XmAb5871‐induced promotion of FcγRIIb phosphorylation and suppression of calcium flux in activated B cells, measured CD86 inhibition in whole blood, and correlated RF and anti−citrullinated protein antibody (ACPA) levels with drug potency. We engrafted RA peripheral blood mononuclear cells (PBMCs) into SCID mice, treated them with XmAb5871, and quantified human total IgG, total IgM, and anti‐tetanus IgG antibody levels in vivo.ResultsB cells from all donors expressed CD19 and FcγRIIb, and the expression of FcγRIIb was higher on naive, but not memory, B cells from donors with RA compared with healthy donors. BCR‐mediated calcium flux was suppressed by XmAb5871 and was associated with FcγRIIb phosphorylation. XmAb5871 inhibited CD86 induction, and the levels of RF and ACPAs did not affect efficacy. XmAb5871 suppressed B cell activation regardless of disease severity. In SCID mice engrafted with PBMCs from a patient with RA, XmAb5871 suppressed humoral responses.ConclusionCoengagement of the BCR complex and FcγRIIb by XmAb5871 inhibits B cell activation and function. The similar potency in patients with RA and healthy donors and the absence of autoantibody interference suggest that XmAb5871 may represent a new therapeutic strategy to suppress autoreactive B cells in RA.