bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synthesis and characterization of polyimides from 4‐(diphenyl phosphine oxide)phenyl pyrromellitic dianhydride
Authors: Bae Yeon‐Ung , Yoon Tae‐Ho 
Published: September 2011

AbstractA novel rigid‐rod type dianhydride monomer with phosphine oxide moiety, 4‐(diphenyl phosphine oxide)phenyl pyrromellitic dianhydride (POPPMDA), was synthesized via the Suzuki coupling reaction of 4‐(diphenyl phosphine oxide)phenyl boronic acid (POBB) and 1‐bromo‐2,3,5,6‐tetramethyl benzene (B4MB), followed by oxidation and cyclodehydration. The monomer was characterized by FTIR, NMR, EA, and melting point analyzer and utilized to synthesize polyimides with diamines such as bis(3‐aminophenyl)phenyl phosphine oxide (mDAPPO) and p‐phenylene diamine (pPDA) by varying their ratio. The polyimides were prepared via a conventional two‐step synthesis: preparation of poly(amic‐acid), followed by solution imidization. The polyimides were characterized by FTIR, NMR, DSC, TGA, and TMA, and their solubility, intrinsic viscosity, and adhesive properties were also evaluated. The polyimides exhibited high Tg (342–362°C), good thermal stability (>500°C), excellent adhesive property (134–107 g/mm), and low CTE (28–17 ppm/°C). © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012
Dystrophic Serotonin Axons in Postmortem Brains from Young Autism Patients
Authors: Azmitia Efrain C. , Singh Jorawer S. , Hou Xiao P. , Wegiel Jerzy 
Published: September 2011

AbstractAutism causes neuropathological changes in varied anatomical loci. A coherent neural mechanism to explain the spectrum of autistic symptomatology has not been proposed because most anatomical researchers focus on point‐to‐point functional neural systems (e.g., auditory and social networks) rather than considering global chemical neural systems. Serotonergic neurons have a global innervation pattern. Disorders Research Program, AS073234, Program Project (JW). Their cell bodies are found in the midbrain but they project their axons throughout the neural axis beginning in the fetal brain. This global system is implicated in autism by animal models and by biochemical, imaging, pharmacological, and genetics studies. However, no anatomical studies of the 5‐HT innervation of autistic donors have been reported. Our review presents immunocytochemical evidence of an increase in 5‐HT axons in postmortem brain tissue from autism donors aged 2.8–29 years relative to controls. This increase is observed in the principle ascending fiber bundles of the medial and lateral forebrain bundles, and in the innervation density of the amygdala and the piriform, superior temporal, and parahippocampal cortices. In autistic donors 8 years of age and up, several types of dystrophic 5‐HT axons were seen in the termination fields. One class of these dystrophic axons, the thick heavily stained axons, was not seen in the brains of patients with neurodegenerative diseases. These findings provide morphological evidence for the involvement of serotonin neurons in the early etiology of autism, and suggest new therapies may be effective to blunt serotonin's trophic actions during early brain development in children. Anat Rec, 2011. © 2011 Wiley‐Liss, Inc.
Metabotropic Glutamate Receptor 5 Upregulation in Children with Autism is Associated with Underexpression of Both Fragile X Mental Retardation Protein and GABAA Receptor Beta 3 in Adults with Autism
Authors: Fatemi S. Hossein , Folsom Timothy D. , Kneeland Rachel E. , Liesch Stephanie B. 
Published: September 2011

AbstractRecent work has demonstrated the impact of dysfunction of the GABAergic signaling system in brain and the resultant behavioral pathologies in subjects with autism. In animal models, altered expression of Fragile X mental retardation protein (FMRP) has been linked to downregulation of GABA receptors. Interestingly, the autistic phenotype is also observed in individuals with Fragile X syndrome. This study was undertaken to test previous theories relating abnormalities in levels of FMRP to GABAA receptor underexpression. We observed a significant reduction in levels of FMRP in the vermis of adults with autism. Additionally, we found that levels of metabotropic glutamate receptor 5 (mGluR5) protein were significantly increased in vermis of children with autism versus age and postmortem interval matched controls. There was also a significant decrease in level of GABAA receptor beta 3 (GABRβ3) protein in vermis of adult subjects with autism. Finally, we found significant increases in glial fibrillary acidic protein in vermis of both children and adults with autism when compared with controls. Taken together, our results provide further evidence that altered FMRP expression and increased mGluR5 protein production potentially lead to altered expression of GABAA receptors. Anat Rec,, 2011. © 2011 Wiley‐Liss, Inc.
Deconstructing Sociability, An Autism‐Relevant Phenotype, in Mouse Models
Authors: Fairless Andrew H. , Shah Rhia Y. , Guthrie Ashley J. , Li Hongzhe , Brodkin Edward S. 
Published: September 2011

AbstractReduced sociability is a core feature of autism spectrum disorders (ASD) and is highly disabling, poorly understood, and treatment refractory. To elucidate the biological basis of reduced sociability, multiple laboratories are developing ASD‐relevant mouse models in which sociability is commonly assessed using the Social Choice Test. However, various measurements included in that test sometimes support different conclusions. Specifically, measurements of time the “test” mouse spends near a confined “stimulus” mouse (chamber scores) sometimes support different conclusions from measurements of time the test mouse sniffs the cylinder containing the stimulus mouse (cylinder scores). This raises the question of which type of measurements are best for assessing sociability. We assessed the test‐retest reliability and ecological validity of chamber and cylinder scores. Compared with chamber scores, cylinder scores showed higher correlations between test and retest measurements, and cylinder scores showed higher correlations with time spent in social interaction in a more naturalistic phase of the test. This suggests that cylinder scores are more reliable and valid measures of sociability in mouse models. Cylinder scores are reported less commonly than chamber scores, perhaps because little work has been done to establish automated software systems for measuring the former. In this study, we found that a particular automated software system performed at least as well as human raters at measuring cylinder scores. Our data indicate that cylinder scores are more reliable and valid than chamber scores, and that the former can be measured very accurately using an automated video analysis system in ASD‐relevant models. Anat Rec, 2011. © 2011 Wiley‐Liss, Inc.
Experimental Strategies for Investigating Psychostimulant Drug Actions and Prefrontal Cortical Function in ADHD and Related Attention Disorders
Authors: Agster Kara L. , Clark Brian D. , Gao Wen‐Jun , Shumsky Jed S. , Wang Huaixing X. , Berridge Craig W. , Waterhouse Barry D. 
Published: September 2011

AbstractAmphetamine‐like psychostimulant drugs have been used for decades to treat a variety of clinical conditions. Methylphenidate (MPH)—RitalinR, a compound that blocks reuptake of synaptically released norepinephrine (NE) and dopamine (DA) in the brain, has been used for more than 30 years in low dose, long‐term regimens to treat attention deficit‐hyperactive disorder (ADHD) in juveniles, adolescents, and adults. Now, these agents are also becoming increasingly popular among healthy individuals from all walks of life (e.g., military, students) and age groups (teenagers thru senior citizens) to promote wakefulness and improve attention. Although there is agreement regarding the primary biochemical action of MPH, the physiological basis for its efficacy in normal individuals and ADHD patients is lacking. Study of the behavioral and physiological actions of clinically and behaviorally relevant doses of MPH in normal animals provides an opportunity to explore the role of catecholamine transmitters in prefrontal cortical function and attentional processes as they relate to normal operation of brain circuits and ADHD pathology. The goal of ongoing studies has been to: (1) assess the effects of low dose MPH on rodent performance in a well characterized sensory‐guided sustained attention task, (2) examine the effects of the same low‐dose chronic MPH administration on task‐related discharge of prefrontal cortical (PFC) neurons, and (3) investigate the effects of NE and DA on membrane response properties and synaptic transmission in identified subsets of PFC neurons. Combinations of these approaches can be used in adolescent, adult, and aged animals to identify the parameters of cell and neural circuit function that are regulated by MPH and to establish an overarching explanation of how MPH impacts PFC operations from cellular through behavioral functional domains. Anat Rec,, 2011. © 2011 Wiley‐Liss, Inc.
Mucosal‐associated invariant T cells promote inflammation and exacerbate disease in murine models of arthritis
Authors: Chiba Asako , Tajima Ryohsuke , Tomi Chiharu , Miyazaki Yusei , Yamamura Takashi , Miyake Sachiko 
Published: September 2011

AbstractObjectiveThe function of mucosal‐associated invariant T (MAIT) cells remains largely unknown. We previously reported an immunoregulatory role of MAIT cells in an animal model of multiple sclerosis. The aim of this study was to use animal models to determine whether MAIT cells are involved in the pathogenesis of arthritis.MethodsMR1−/− and MR1+/+ DBA/1J mice were immunized with bovine type II collagen (CII) in complete Freund's adjuvant to trigger collagen‐induced arthritis (CIA). To assess CII‐specific T cell recall responses, lymph node cells from mice with CIA were challenged with CII ex vivo, and cytokine production and proliferation were evaluated. Serum levels of CII‐specific antibodies were measured by enzyme‐linked immunosorbent assay. Collagen antibody–induced arthritis (CAIA) was induced in MR1−/− and MR1+/+ C57BL/6 mice by injection of anti‐CII antibodies followed by injection of lipopolysaccharide. To demonstrate the involvement of MAIT cells in arthritis, we induced CAIA in MR1−/− C57BL/6 mice that had been reconstituted with adoptively transferred MAIT cells. MAIT cell activation in response to cytokine stimulation was investigated.ResultsThe severity of CIA was reduced in MR1−/− DBA/1J mice. However, T and B cell responses to CII were comparable in MR1−/− and MR1+/+ DBA/1J mice. MR1−/− C57BL/6 mice were less susceptible to CAIA, and reconstitution with MAIT cells induced severe arthritis in MR1−/− C57BL/6 mice, demonstrating an effector role of MAIT cells in arthritis. MAIT cells became activated upon stimulation with interleukin‐23 (IL‐23) or IL‐1β in the absence of T cell receptor stimuli.ConclusionThese results indicate that MAIT cells exacerbate arthritis by enhancing the inflammation.
Ultrasonographic evaluation of medial radial displacement of the medial meniscus in knee osteoarthritis
Authors: Kawaguchi Kei , Enokida Makoto , Otsuki Ryoji , Teshima Ryota 
Published: September 2011

AbstractObjectiveTo evaluate medial radial displacement (MRD) of the medial meniscus in osteoarthritic (OA) and normal knees, with and without weight bearing, using ultrasonography (US), and to prospectively evaluate the time course of changes in MRD in OA knees.MethodsThe study subjects were 78 patients with OA of the knee (69% female; mean age 66.4 years) and 20 healthy, asymptomatic subjects (70% female; mean age 64.5 years) who served as a control group. The OA stage was determined according to the Kellgren/Lawrence (K/L) radiographic grading system. US measurement of MRD was performed with subjects in the supine and standing positions. With the exception of subjects who dropped out, 58 OA knees (followup rate 74%) were evaluated at baseline and ∼1 year later.ResultsThe medial meniscus was significantly displaced radially by weight bearing in control knees (P < 0.001) and in knees with K/L grades 1–3 OA (P < 0.01 for each comparison). MRD in either the supine or the standing position was not significantly different between the control knees and the K/L grade 1 knees, but significant differences were noted between the control knees and K/L grade 2 or more severe OA knees (P < 0.01 for each comparison). MRD of the medial meniscus had increased significantly on followup in all knees (P < 0.05 for each comparison) excluding K/L grade 4 knees in the standing position.ConclusionMRD of the medial meniscus increased with weight bearing and during followup. These findings suggest a close association between extraarticular displacement of the medial meniscus and progression of OA.
Noncardiac vascular disease in rheumatoid arthritis: Increase in venous thromboembolic events?
Authors: Bacani A. Kirstin , Gabriel Sherine E. , Crowson Cynthia S. , Heit John A. , Matteson Eric L. 
Published: September 2011

AbstractObjectiveTo investigate the incidence of noncardiac vascular disease in a community‐based incidence cohort of patients with rheumatoid arthritis (RA) and compare it to that in the general population and to investigate trends in the incidence of noncardiac vascular disease in patients with RA.MethodsA population‐based inception cohort of patients with incident RA between January 1, 1980 and December 31, 2007 in Olmsted County, Minnesota and a cohort of non‐RA subjects from the same population base was assembled and followed up until December 31, 2008. Venous thromboembolic, cerebrovascular, and peripheral arterial events were ascertained by medical record review.ResultsThe study population included 813 patients with RA with a mean ± SD age of 55.9 ± 15.7 years (68% women) and an average length of followup of 9.6 ± 6.9 years. Compared to non‐RA subjects of similar age and sex, patients diagnosed as having RA between 1995 and 2007 had a higher incidence (%) of venous thromboembolism (cumulative incidence ± SE 6.7 ± 1.7 versus 2.8 ± 1.1, respectively; P = 0.005) but similar rates of cerebrovascular and peripheral arterial events. Among patients with RA, the incidence of venous thromboembolic, cerebrovascular, and peripheral arterial events was similar in the 1995–2007 time period compared to the 1980–1994 time period.ConclusionOur findings indicate that the incidence of venous thromboembolism is increased in patients with RA compared to non‐RA subjects. The incidence of cerebrovascular events and peripheral vascular disease events is similar in patients with RA compared to non‐RA subjects. Among patients with RA, the incidence of noncardiac vascular disease has remained stable in recent decades.
Protease‐activated receptor 2, rather than protease‐activated receptor 1, contributes to the aggressive properties of synovial fibroblasts in rheumatoid arthritis
Authors: Xue Meilang , Chan Yee‐Ka Agnes , Shen Kaitlin , Dervish Suat , March Lyn , Sambrook Philip N. , Jackson Christopher J. 
Published: September 2011

AbstractObjectiveTo investigate whether protease‐activated receptor 1 (PAR‐1) and/or PAR‐2 promotes the invasiveness/proliferation of synovial fibroblasts (SFs) and to determine the signaling mechanisms of these pathways.MethodsSFs were isolated from the synovial tissue of patients with rheumatoid arthritis (RA), patients with osteoarthritis (OA), and PAR‐1– or PAR‐2–knockout (KO) mice. Expression of PAR‐1 and PAR‐2 was detected by immunofluorescence and Western blotting. The invasion and proliferation of SFs were measured by invasion assay and MTT assay, respectively. Matrix metalloproteinase 2 (MMP‐2) and MMP‐9 were detected by zymography, and cytokines were measured by enzyme‐linked immunosorbent assay.ResultsPAR‐1 and PAR‐2 were colocalized with SFs in RA and OA synovium and, to a considerably lesser extent, in normal synovium. Inhibition of PAR‐2 by small interfering RNA (siRNA) inhibited RASF invasion and proliferation, whereas blocking of PAR‐1 by siRNA had the reverse effects. SFs from PAR‐2–KO mice exhibited slower rates of proliferation and invasion. SFs from PAR‐1–KO mice produced less MMP‐2 and, in response to tumor necrosis factor α (TNFα) stimulation, had increased MMP‐9 secretion when compared to SFs from wild‐type and PAR‐2–KO mice. Inhibition of PAR‐1, but not PAR‐2, stimulated the secretion of interleukin‐17 (IL‐17) and TNFα by RASFs. Furthermore, PAR‐1 and PAR‐2 had opposing effects on the activation of ERK, p38, and NF‐κB.ConclusionActivation of PAR‐1 stimulates MMP‐2 secretion, inhibits RASF growth and invasion, and decreases production of IL‐17 and TNFα by RASFs, whereas activation of PAR‐2 stimulates RASF growth and invasion and increases production of TNFα. Thus, although PAR‐1 and PAR‐2 are coexpressed by RASFs, PAR‐2 alone appears to be responsible for the aggressive properties of RASFs and is likely to contribute to the pathologic progression of RA.
Heterogeneous nuclear RNPs as targets of autoantibodies in systemic rheumatic diseases
Authors: Op De Beéck Katrijn , Maes Liesbeth , Van den Bergh Karolien , Derua Rita , Waelkens Etienne , Van Steen Kristel , Vermeersch Pieter , Westhovens René , De Vlam Kurt , Verschueren Patrick , Hooijkaas Herbert , Blockmans Daniel , Bossuyt Xavier 
Published: September 2011

AbstractObjectiveTo investigate the abundance of autoantibodies to heterogeneous nuclear RNPs (hnRNPs) in systemic rheumatic diseases.MethodsRecombinant human hnRNPs A1, B1, C1, E1, F, Gi, H1, I, K, and P2 were prepared. Antibodies to these antigens were determined by Western blotting and by enzyme‐linked immunosorbent assay (ELISA) (for hnRNPs B1, E1, F, and H1) in serum samples obtained from patients with chronic fatigue syndrome (control subjects) and from patients with various connective tissue diseases.ResultsWestern blotting analysis in 106 control subjects and 298 patients with a connective tissue disease revealed that antibodies to all tested hnRNP antigens, except hnRNP Gi, were significantly more prevalent in patients with Sjögren's syndrome (SS) than in control subjects. The highest reactivity was observed for hnRNPs B1, E1, F, and H1 (reactivity in >45% of patients with SS and in 2.8% of control subjects). Reactivity with hnRNPs B1, E1, F, and H1 was also evaluated by ELISA in 89 control subjects and 228 patients with a connective tissue disease. Reactivity with at least 2 of the 4 tested antigens was observed in 1.1% of control subjects, 16% of patients with systemic lupus erythematosus (SLE), and 18% of patients with SS. Reactivity with at least 3 of the 4 antigens was observed in 0% of the control subjects, 3.2% of patients with SLE, and 15% of patients with SS.ConclusionSeveral hnRNPs are target antigens in SS. The combined presence of antibodies to several hnRNPs was strongly associated with connective tissue disease in general and with SS in particular.
Mechanisms involved in enhancement of the expression and function of aggrecanases by hyaluronan oligosaccharides
Authors: Ariyoshi Wataru , Takahashi Nobunori , Hida Daisuke , Knudson Cheryl B. , Knudson Warren 
Published: September 2011

AbstractObjectiveSmall hyaluronan (HA) oligosaccharides serve as competitive receptor antagonists to displace HA from the cell surface and induce cell signaling events. In articular chondrocytes, this cell signaling is mediated by the HA receptor CD44 and induces stimulation of genes involved in matrix degradation, such as matrix metalloproteinases (MMPs) as well as matrix repair genes including type II collagen, aggrecan, and HA synthase 2. The objective of this study was to determine changes in the expression and function of aggrecanases after disruption of chondrocyte CD44–HA interactions.MethodsBovine articular chondrocytes or bovine cartilage tissue was pretreated with a variety of inhibitors of major signaling pathways prior to the addition of HA oligosaccharides. Changes in aggrecanase were monitored by real‐time reverse transcription–polymerase chain reaction and Western blot analyses of ADAMTS‐4, ADAMTS‐5, and aggrecan proteolytic fragments. To test the interactions between ADAMTS‐4 and membrane type 4 MMP (MT4‐MMP), protein lysates purified from stimulated chondrocytes were subjected to coimmunoprecipitation.ResultsDisruption of chondrocyte CD44–HA interactions with HA oligosaccharides induced the transcription of ADAMTS‐4 and ADAMTS‐5 in a time‐ and dose‐dependent manner. The association of glycosyl phosphatidylinositol–anchored MT4‐MMP with ADAMTS‐4 was also induced in articular chondrocytes by HA oligosaccharides. Inhibition of the NF‐κB pathway blocked HA oligosaccharide‐mediated stimulation of aggrecanases.ConclusionDisruptive changes in chondrocyte–matrix interactions by HA oligosaccharides induce matrix degradation and elevate aggrecanases via the activation of the NF‐κB signaling pathway.
Soluble VE‐cadherin in rheumatoid arthritis patients correlates with disease activity: Evidence for tumor necrosis factor α–induced VE‐cadherin cleavage
Authors: Sidibé Adama , Mannic Tiphaine , Arboleas Mélanie , Subileau Mariela , Gulino‐Debrac Danielle , Bouillet Laurence , Jan Mary , Vandhuick Thibault , Le Loët Xavier , Vittecoq Olivier , Vilgrain Isabelle 
Published: September 2011

AbstractObjectiveRheumatoid arthritis (RA) is a chronic, systemic inflammatory disorder that principally attacks synovial joints. However, accelerated atherosclerosis and increased cardiovascular morbidity and mortality are major clinical consequences of endothelial dysfunction in RA patients. Tumor necrosis factor α (TNFα) is the major mediator of inflammation in RA, related to vascular injury by targeting VE‐cadherin, an endothelium‐specific adhesion molecule of vital importance for endothelium integrity and angiogenesis. We undertook this study to examine the mechanisms regulating VE‐cadherin processing by TNFα and their occurrence in RA.MethodsHuman umbilical vein endothelial cells were used in primary culture and treated with recombinant TNFα to study VE‐cadherin cleavage. Cell lysates and conditioned media were analyzed by Western blotting for VE‐cadherin cytoplasmic domain and extracellular domain (VE‐90) generation, respectively. VE‐90 was analyzed at baseline and at the 1‐year followup in sera from 63 RA patients (from the Very Early Rheumatoid Arthritis cohort) with disease duration of <6 months.ResultsTNFα induced a time‐dependent shedding of VE‐90 in cell media. This effect was prevented by tyrosine kinase inhibitors (genistein and PP2) or by knocking down Src kinase. In contrast, tyrosine phosphatase blockade enhanced VE‐cadherin cleavage, confirming the requirement of tyrosine phosphorylation processes. In addition, using the matrix metalloproteinase (MMP) activator APMA and the MMP inhibitor GM6001, we demonstrated that MMPs are involved in TNFα‐induced VE‐cadherin cleavage. Of major importance, VE‐90 was detected in sera from the 63 RA patients and was positively correlated with the Disease Activity Score at baseline and after 1‐year followup.ConclusionThese findings provide the first evidence of VE‐cadherin proteolysis upon TNFα stimulation and suggest potential clinical relevance of soluble VE‐cadherin in management of RA.