bluuebunny/crossref_metadata_2025 huggingface dataset:
Re-attachment of the tuberosities of the humerus following hemiarthroplasty for four-part fracture
Authors: Abu-Rajab R. B. , Stansfield B. W. , Nunn T. , Nicol A. C. , Kelly I. G.
Published: October 2006

This study evaluated the effect on movement under load of three different techniques for re-attachment of the tuberosities of the humerus using test sawbones. In the first, the tuberosities were attached both to the shaft and to each other, with one cerclage suture through the anterior hole in the prosthesis. The second technique was identical except for omission of the cerclage suture and in the third the tuberosities were attached to the prosthesis and to the shaft. An orthogonal photogrammetric system allowed all segments to be tracked in a 3D axis system. The humeri were incrementally-loaded in abduction, and the 3D linear and angular movements of all segments were calculated. Displacement between the tuberosities and the shaft was measured.

The first and second techniques were the most stable constructs, with the third allowing greater separation of fragments and angular movement. Separation at the midpoint of the tuberosities was significantly greater using the latter technique (p < 0.05). The cerclage suture added no further stability to the fixation.
Corticotropin releasing hormone and the immune/inflammatory response
Authors: Mastorakos George , Karoutsou Eftychia I , Mizamtsidi Maria
Published: October 2006

Hypothalamic corticotropin-releasing hormone (CRH) acts as the major physiologic ACTH secretagog. Moreover, CRH is distributed in the brain and spinal cord, adrenal medulla, testes, ovaries, gastrointestinal tract, pancreas, myometrium, endometrium, placenta, and diverse inflammatory sites. Immunoreactive CRH has been found in the cytoplasm of immune accessory cells (macrophages, endothelial cells, and tissue fibroblasts), and in inflammatory sites of both acute and chronic inflammation (synovial lining cell layers and blood vessels from the joints of patients with rheumatoid arthritis and osteoarthritis). Additionally, the local presence of CRH in the uveitic eyes, cytoplasm of inflammatory cells (macrophages, lymphocytes, and polymorphonuclear cells) infiltrating the iris, ciliary body, vitreous, retina, and choroid appears to be of pivotal importance in the process of experimental autoimmune uveoretinitis. Traditionally, hypothalamic CRH has been considered to act indirectly in an anti-inflammatory fashion, since the end product of the hypothalamic–pituitary–adrenal axis is cortisol, a well-known anti-inflammatory compound. However, CRH produced at peripheral inflammatory sites has been shown to participate in an autocrine/paracrine stimulation of inflammation. Thus, CRH may have a peripheral, primarily activating role on the immune system. The mechanisms of the CRH-mediated component of the immune/inflammatory response are still unclear. CRH in inflammatory sites seems to be involved in the activation of the Fas/Fas ligand system. Furthermore, locally produced embryonic and endometrial CRH plays a role in both the aseptic inflammatory process of implantation and the anti-rejection process that protects the fetus from the maternal immune system. There are two types of G-protein-coupled CRH receptors (CRH-R1 and CRH-R2). Pyrrolopyrimidine compounds, such as antalarmin, have been developed as CRH-R1 receptor antagonists. Confirming the peripheral pro-inflammatory actions of CRH, antalarmin has been shown to suppress experimental aseptic inflammation. Thus, antalarmin may represent the first in a new class of anti-inflammatory agents operating through CRH-R1. Studies of CRH genetics have provided new insights on the pathogenesis of rheumatoid arthritis in humans. DNA variation across the CRH gene-containing region has been examined in families with multiple cases of rheumatoid arthritis. Transmission Disequilibrium Test analysis showed significant association at the CRH locus.
Paternal age, size at birth, and size in young adulthood – risk factors for schizophrenia
Authors: Rasmussen Finn
Published: October 2006

It is appropriate to consider schizophrenia a neurodevelopmental disorder with its pathogenesis going back to gestation and early childhood. Schizophrenia is a rare disease and large cohorts are needed to study its etiology. The aim of this paper is to review the results of recent Swedish record-linkage studies with a focus on: (i) measures of fetal and childhood growth in relation to schizophrenia in adulthood and (ii) paternal age in relation to schizophrenia. A record-linkage was created between national registers, including the Medical Birth Register, the Military Service Conscription Register, and the Inpatient Hospital Discharge Register. More than 700 000 subjects born between 1973 and 1980 were followed in these registers from birth to 31 December 2001/2002. The results showed no evidence of an association between birth weight and schizophrenia. An association of birth length with schizophrenia was observed, with short babies showing the highest risk. Short stature and low BMI in young adulthood were associated with increased risk. Short babies who became tall, or developed high BMI as adults, were not at increased risk. In fully adjusted analyses, the risk of schizophrenia was 4.62 (95% confidence interval : 2.28; 9.36) times higher in subjects whose fathers were ≥50 years old and at time of conception than in subjects whose fathers were 21–24 years old. Growth and development in fetal life and childhood are influencing the risk of schizophrenia in adulthood, but the underlying causal pathways are still unknown. De novo mutations in the germ cells of older fathers may play a causal role in the etiology of some cases of schizophrenia.
L2 Tasks and Orientation to Form
Authors: Adams Rebecca
Published: October 2006

Task-based language teaching has been advocated as a means of promoting learning through learner interactions in the classroom. However, characteristics of the design and implementation of communicative tasks have been shown to influence learner orientation to form. One task characteristic that may affect learner attention to form, modality, is examined here to determine whether it influences learners' tendency to focus on second language form. Forty-four adult ESL learners engaged in information gap tasks targeted at specific second language forms that required the learners to collaboratively achieve both an oral and a written outcome. Analysis of orientation to form in both spoken and written sections of the task indicated that task modality plays a role in influencing learner orientation to form.
Taking Text to Task
Authors: Byrnes Heidi , Crane Cori , H. Maxim Hiram , Sprang Katherine A.
Published: October 2006

This article argues that the construct of task can provide a principled and effective foundation for the development of extended, multi-year curricula and pedagogies for second/foreign language learning of adults. That assertion is made with an important condition: "task" must be expanded, both theoretically and empirically, toward issues that arise in conjunction with textuality and literacy rather than being grounded primarily in psycho linguistic, sentence-oriented processing considerations, as original proposals by Long and Crookes (1992) had suggested.

The article presents that overall theoretical argument and then describes how genre-based tasks have been used (1) for selection and sequencing decisions within an existing contentoriented collegiate curriculum in the German Department at Georgetown University; (2) as a way to inform pedagogical choices that target advanced levels of L2 ability, particularly the crucial area of vocabulary development; and (3) to devise genre-based tasks that assess L2 learners' language abilities and content knowledge across the curriculum and also help to further specify learning objectives and curricular choices.
Full‐scale evaluation of biological nitrogen removal in the step‐feed activated sludge process
Authors: Fillos John , Diyamandoglu Vasil , Carrio Luis A. , Robinson Lawrence
Published: October 2006

Establishment of nitrification and denitrification in an existing conventional, step‐feed activated sludge plant designed for suspended solids and carbonaceous biochemical oxygen demand removal was evaluated in a full‐scale study at the Tallman Island Water Pollution Control Plant in New York City. One of four biological treatment batteries consisting of an aeration tank and two rectangular secondary clarifiers was isolated from the rest of the plant and was used for the study. Nitrification rates and their temperature dependency were determined using NH3‐N and NO3‐N profiles developed along the aeration tank during the summer and winter months. The data suggested the occurrence of simultaneous nitrification and denitrification in the aeration tank. Virtually complete denitrification was observed within the sludge blanket of the secondary clarifier.
Ultraviolet disinfection of filtered activated sludge effluent for reuse applications
Authors: Braunstein Jeffrey L. , Loge Frank J. , Tchobanoglous George , Darby Jeannie L.
Published: October 2006

An ultraviolet (UV) disinfection system was assessed in terms of the most stringent U.S. wastewater reuse standards. The UV inactivation of total and fecal coliform bacteria and seeded MS2 coliphages in filtered activated sludge effluent was tested continuously for 22 weeks. The most stringent coliform criterion, that the 7‐day median not exceed 2.2 per 100 mL, was met consistently in effluent exposed to an average UV dose of 168 and 112 mW/cm2 · s for total and fecal coliforms, respectively. MS2 coliphages were more resistant to UV disinfection than the coliform group. Both the point source summation (PSS) and bioassay methods were used to estimate UV dose in the system. For a 95% confidence interval, the PSS method resulted in an equivalent estimate of UV dose when compared with the bioassay method.
Feasibility, system design, and economic evaluation of radiolytic degradation of 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin on soil
Authors: Hilarides Roger J. , Gray Kimberly A. , Guzzetta Joseph , Cortellucci Norma , Sommer Christopher
Published: October 2006

This research shows that gamma irradiation is both a technically and economically feasible method to degrade chlorinated dioxins on soil. Approximately 99% degradation of dioxin on a model soil was achieved using gamma radiation at a dose of 800 kGy. In addition, this research determined the initial pathway of destruction, identified several controlling parameters, and developed a mass balance on degradation. The general applicability of this model behavior was successfully tested in a native contaminated soil where nearly 75% of the dioxin was destroyed at a dose of 450 kGy. Through a theoretical and conceptual understanding of radiolysis in soil, a sound basis for engineering design was established. Gamma radiation sources are commercially available, and this research outlines a new application of an established technology. A number of irradiator designs are proposed, and preliminary economic estimates are made to demonstrate that radiolysis can be a real alternative to incineration.
Nocardia control in activated sludge by classifying selectors
Authors: Pagilla Krishna R. , Jenkins David , Kido Wendell H.
Published: October 2006

Laboratory‐ and full‐scale experiments investigated the use of a classifying selector for Nocardia control in activated sludge. A classifying selector is a device that produces surface foam from the bulk mixed liquor and then removes it. The laboratory‐scale classifying selector activated sludge system operating at a 10‐day mean cell residence time (MCRT), pH = 6.6, dissolved oxygen (DO) = 8.0 mg/L, and temperature = 24°C produced mixed liquor Nocardia levels lower than an unfoamed control activated sludge plant. Addition of low doses (0.5 mg/L) of a readily biodegradable nonionic surfactant (NEODOL 25–7) to the classifying selector system just before foaming reduced the mixed liquor Nocardia levels to below those achieved in a classifying selector system without surfactant addition. A classifying selector installed in the RAS channel combined with selective foam wasting from the mixed liquor channels and secondary clarifiers in a full‐scale activated sludge plant reduced Nocardia levels below those achieved during operation without a classifying selector.
Phylogenetic analyses within three sections of the genus Vicia
Authors: Sakowicz Tomasz , Cieślikowski Tomasz
Published: October 2006

The averaged genomic similarities based on multilocus randomly amplified polymorphic DNA (RAPD) were calculated for eight species representing three sections of the genus Vicia: faba, bithynica and narbonensis. The frequency of appearance of the sequences corresponding to 25 decamers selected at random from genomes of different Fabace species was checked, and a high correlation with the frequency observed for Vicia allowed us to assume their similar weight in typing Vicia species. The RAPD-based similarity coefficients compared with those related to whole genome hybridization with barley rDNA and those based on restriction fragment length polymorphism (RFLP) revealed similar interspecies relationships. The averaged RAPD-based similarity coefficient (Pearson’s) was 0.68 for all the species, and was sectionspecific: 0.43 (bithynica), 0.50 (faba) and 0.73 (narbonensis). The averaged similarity coefficient for V. serratifolia (0.63) placed it apart from the rest (0.75) of its section. The results correspond to the interspecies relationships built upon non-genetic data. The averaged similarity coefficient for particular RAPD was related to the presence and type of tandemly repeated motif in a primer: 0.7–0.8 for heterodimers (GC, AG, CA, GT, CT), 0.5–0.6 for homodimers (CC, GG) and 0.6 for no repeat, indicating the sensitivity of diversity range to the type of target sequences.
When a trauma becomes a key to identity: enhanced integration of trauma memories predicts posttraumatic stress disorder symptoms
Authors: Berntsen Dorthe , Rubin David C.
Published: October 2006

The Centrality of Event Scale (CES) measures the extent to which a traumatic memory forms a central component of personal identity, a turning point in the life story and a reference point for everyday inferences. In two studies, we show that the CES is positively correlated with severity of PTSD symptoms, even when controlling for measures of anxiety, depression, dissociation and self‐consciousness. The findings contradict the widespread view that poor integration of the traumatic memory into one's life story is a main cause of PTSD symptoms. Instead, enhanced integration appears to be a key issue. Copyright © 2006 John Wiley & Sons, Ltd.
Anionenkoordination mit Amidliganden
Authors: Kang Sung Ok , Begum Rowshan Ara , Bowman‐James Kristin
Published: October 2006

Die Anionenerkennung ist ein aktives Forschungsgebiet der supramolekularen Chemie. Mittlerweile stehen ausreichend viele Strukturdaten zur Verfügung, um die Anionenkoordination formal nach Koordinationszahl und Koordinationsgeometrie einzuteilen, und zwar auf Basis der Wasserstoffbrücken zwischen Wirt (Ligand) und Gast (Anion). In diesem Kurzaufsatz wird nur eine Anionenrezeptorart behandelt, nämlich Amidliganden. Für fünf Anionenformen werden die Strukturdaten nach der Koordinationszahl aufgelistet und Gemeinsamkeiten innerhalb einer gegebenen Anionentopologie ermittelt. Dabei zeigen sich Ähnlichkeiten zwischen der Koordination von Anionen und der von Übergangsmetallionen.
Sequential interpenetrating polymer network based on styrene butadiene rubber and polyalkyl methacrylates
Authors: Patri M. , Reddy C. V. , Narasimhan C. , Samui A. B.
Published: October 2006

A series of sequential interpenetrating polymer network (IPNs) based on styrene butadiene rubber (SBR) and polyalkyl (methyl, ethyl, and butyl) methacrylates have been prepared by using tetraethylene glycol dimethacrylate as crosslinker. The IPNs were characterized by infrared spectrophotometer, dynamic mechanical analyzer, thermogravimetric analyzer, and swelling study. IPNs have exhibited higher tensile properties compared with pure SBR. IPNs based on PMMA have shown higher tensile strength compared with others. Dynamic mechanical analysis has shown that the IPNs have superior dynamic properties than SBR. Because of IPN formation, tan δ peak shifted inward between SBR and acrylates. Although the magnitude of tan δ decreased, the peaks were broadened because of micro heterogeneous phase separation. At higher concentration of methacrylate, splitting in tan δ peak was noticed because of phase separation. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 1120–1126, 2007
Morphology, structure, and kinetic analysis of nonisothermal cold‐ and melt‐crystallization of syndiotactic polystyrene
Authors: Cai Jiali , Han Ying
Published: October 2006

Nonisothermal cold‐ and melt‐crystallization of syndiotactic polystyrene (sPS) were carefully carried out by Perkin–Elmer Diamond differential scanning calorimetry, polarized optical microcopy (POM), and wide angle X‐ray diffraction. The experimental data subjected to the two types of processing were thoroughly analyzed on the basis of Avrami, Tobin, Ziabicki, and combination of Avrami and Ozawa models. Avrami, Tobin, and Ziabicki analyses indicate that nonisothermal cold‐crystallization (A) characterizes smaller Avami and Tobin exponent and larger Ziabicki kinetic crystallizability index G than those obtained from nonisothermal melt‐crystallization (B) possibly due to the existence of partially ordered structures in the quenched samples. Kissinger and the differential isoconversional method (DICM) of Friedman's were utilized to obtain effective energy barrier of A, in good agreement with that obtained by using Arrhenius equation to analyze the isothermal cold‐crystallization, indicating that Kissinger and Friedman equations can be applied to obtain activation energy from A of sPS. X‐ray diffraction analysis indicates that cold‐crystallization mainly produces α‐type crystal but for melt‐crystallization the contents of α‐type and β‐type crystals depend on the cooling rates. The POM also indicates the difference of end morphology of the sample between A and B. At the same time, the DICM of Friedman's was applied to analyze experimental data of B, which were divided into two groups with 20 K/min as the threshold, and it was found that the formation of β‐type crystal possesses larger absolute value of effective activation barrier than the formation of α‐type crystal. © 2006Wiley Periodicals, Inc. J Appl Polym Sci 103: 1311–1324, 2007
Effect of compounding procedure on mechanical properties and dispersed phase morphology of poly(lactic acid)/polycaprolactone blends containing peroxide
Authors: Semba Takeshi , Kitagawa Kazuo , Ishiaku Umaru S. , Kotaki Masaya , Hamada Hiroyuki
Published: October 2006

Side feeding technique was applied to poly (lactic acid) (PLA)/polycaprolactone (PCL) blends containing peroxide. Feeding procedures attempted were blanket and split feeding. In the former procedure, all the materials were fed into the main hopper at once. On the other hand, the feeding of materials was split by using main hopper and side feeder in the later procedure. The results indicated that static tensile properties were not dependent on feeding procedure, but the impact strength was superior in the case of the split feeding samples. It is noteworthy that the impact strength of the split feeding sample was considerably affected as it was four times better. Coarse dispersions such as continuous filament and layer dispersions were formed in the blend specimens without peroxide. On the other hand, fine dispersions were formed in the blend specimens containing peroxide which served as compatibilizer in this blend system. Peroxide addition through the side feeder brought about fine dispersions, promoted adhesion at the interface, and increased viscous nature of the PCL phase. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 1066–1074, 2007
Novel high performance copper clad laminates based on bismaleimide/aluminium borate whisker hybrid matrix
Authors: Gu Aijuan , Liang Guozheng
Published: October 2006

A novel method to prepare high performance copper clad laminates (CCLs) was developed by using bismaleimide/aluminum borate (Al18B4O33) whisker hybrid as the matrix. The typical important properties such as thermal, mechanical, and dielectric properties of CCLs were investigated in detail. Results show that the incorporation of surface treated Al18B4O33 whiskers with suitable concentration can noticeably increase the flexural strength and modulus, interlayer shear strength, the heat distortion temperature, as well as dielectric properties of the CCLs. Intensive studies show that the improved concrete strength of the matrix and that in the direction of thickness of CCLs are contributed to the noticeable improvement of mechanical properties of CCLs by using the hybrid matrix. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 1325–1331, 2007
Berberine finishing for developing antimicrobial nylon 66 fibers: % exhaustion, colorimetric analysis, antimicrobial study, and empirical modeling
Authors: Son Young‐A. , Kim Byung‐Soon , Ravikumar K. , Kim Tae‐Kyeong
Published: October 2006

Berberine, a natural cationic colorant was successfully employed onto nylon 66 fiber in this research. The effects of three important variables, namely pH, temperature, and liquor ratio were examined on the % exhaustion, color strengths, and color yields of the sample. It has been employed in antimicrobial finishing as a natural agent on nylon 66 due to its characteristics of cationic quaternary ammonium salt. Antimicrobial activity of the sample was studied against Staphylococcus aureus (ATCC 6538) and Klebsiella pneumoniae (ATCC 4352) according to test method KS K 0693‐2001 and the corresponding berberine finished sample showed very effective antimicrobial functions showing about 99.9% of bacterial reduction against above‐mentioned two bacteria. The maximum % exhaustion, color strengths, and color yields were obtained at 98 °C, alkaline condition (pH 11) and lower liquor ratio (20 : 1). An appropriate predictable empirical models were also developed using Excel solver function incorporating interaction effects of all variables to predict the % exhaustion, color strength(K/S), and the satisfactory results (R2 > 0.99) were obtained. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 1175–1182, 2007
Electron‐beam‐induced crosslinking of natural rubber/acrylonitrile–butadiene rubber latex blends in the presence of ethoxylated pentaerythritol tetraacrylate used as a crosslinking promoter
Authors: Chowdhury Rajesh
Published: October 2006

A natural rubber latex, an acrylonitrile–butadiene rubber latex, and their 50: 50 blends were exposed to an electron beam in air. A polyfunctional monomer, ethoxylated pentaerythritol tetraacrylate, was used as a crosslinking promoter. Cast films from the irradiated systems were characterized for their gel contents, swelling properties, and tensile strength. An increase in the radiation dose from 0 to 500 kGy resulted in increased crosslinking, as measured by an increase in the gel content and better swelling resistance. The effect of the polyfunctional monomer, ethoxylated pentaerythritol tetraacrylate, as a crosslinking promoter was studied with infrared spectros copy. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 1206–1214, 2007
Habitat mapping and conservation analysis to identify critical streams for Arizona's native fish
Authors: Turner Dale S. , List Michael D.
Published: October 2006

Arizona's native fish species are among the most imperilled fauna in North America. Knowing the current distribution of native fish and their habitat is critical to their management and conservation, but the last detailed mapping effort was more than 30 years ago and pre‐dated computer mapping techniques.

Current distribution of 34 native fish species was modelled by identifying perennial stream segments for which species presence had been documented. A composite of these single‐species maps displays a pattern of species richness that can inform conservation, especially when overlaid with maps of management status or invasive species.

The map overlays suggest that conservation priorities should include Eagle Creek, the Verde River and its tributaries, Aravaipa Canyon, the Virgin River and Black Draw, which together hold 63% of native fish species. Of the 32 streams that support five or more native species, 28 have at least one non‐native fish species, indicating that a more aggressive programme of removing non‐natives may be critical to maintaining those native populations.

The U.S. Forest Service and Native American tribes administer the majority of occupied stream habitat (30% and 27%, respectively). While private lands hold the third‐highest amount of occupied habitat (19%), they control streams occupied by the greatest total number of native species (30). Conservationists should work more with private land owners, while also coordinating efforts with the U.S. Forest Service and North American tribes.

These data are publicly available (on the Internet, URL: www.azconservation.org) to encourage refinement and use.

Copyright © 2006 John Wiley & Sons, Ltd.
Valproic acid‐induced fetal malformations are reduced by maternal immune stimulation with granulocyte‐macrophage colony‐stimulating factor or interferon‐γ
Authors: Hrubec Terry C. , Yan Mingjin , Ye Keying , Salafia Carolyn M. , Holladay Steven D.
Published: October 2006

Valproic acid, a drug commonly used to treat seizures and other psychiatric disorders, causes neural tube defects (NTDs) in exposed fetuses at a rate 20 times higher than in the general population. Failure of the neural tube to close during development results in exencephaly or anencephaly, as well as spina bifida. In mice, nonspecific activation of the maternal immune system can reduce fetal abnormalities caused by diverse etiologies, including diabetes‐induced NTDs. We hypothesized that nonspecific activation of the maternal immune system with interferon‐γ (IFN‐γ) and granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) could reduce valproic acid (VA)‐induced defects as well. Female CD‐1 mice were given immune stimulant prebreeding: either IFN‐γ or GM‐CSF. Approximately half of the control and immune‐stimulated pregnant females were then exposed to 500 mg/kg VA on the morning of gestational day 8. The incidence of developmental defects was determined on gestational day 17 from at least eight litters in each of the following treatment groups: control, VA only, IFN‐γ only, IFN‐γ + VA, GM‐CSF only, and GM‐CSF + VA. The incidence of NTDs was 18% in fetuses exposed to VA alone, compared to 3.7% and 2.9% in fetuses exposed to IFN‐γ + VA, or GM‐CSF + VA respectively. Ocular defects were also significantly reduced from 28.0% in VA exposed groups to 9.8% in IFN‐γ + VA and 12.5% in GM‐CSF + VA groups. The mechanisms by which maternal immune stimulation prevents birth defects remain unclear, but may involve maternal or fetal production of cytokines or growth factors which protect the fetus from the dysregulatory effects of teratogens. Anat Rec Part A, 2006. © 2006 Wiley‐Liss, Inc.
A novel autoantibody to a 155‐kd protein is associated with dermatomyositis
Authors: Targoff Ira N. , Mamyrova Gulnara , Trieu Edward P. , Perurena Osvaldo , Koneru Bhanu , O'Hanlon Terrance P. , Miller Frederick W. , Rider Lisa G.
Published: October 2006

Objective

In polymyositis and dermatomyositis (DM), identified autoantibodies occur in <50% of adult patients and in a smaller proportion of children. This study was undertaken as part of a larger effort to define novel autoantibodies that assist in the clinical evaluation of myositis.

Methods

Sera from children and adults satisfying criteria for idiopathic inflammatory myopathies and from patients with other connective tissue diseases (CTDs), patients with noninflammatory myopathies, and healthy individuals were tested for autoantibodies by immunoprecipitation (IP). A previously unrecognized autoantibody that immunoprecipitated a 155‐kd protein along with a weaker 140‐kd protein was seen. When the presence of this anti‐p155 autoantibody in test sera was suggested based on IP results, it was confirmed by immunoblotting of immunoprecipitates.

Results

Sera from 51 of 244 myositis patients (21%), including 30 with juvenile DM (29%), 5 with juvenile CTD–associated myositis (33%), 8 with adult DM (21%), 6 with cancer‐associated DM (75%), and 2 with adult CTD–associated myositis (15%), were found to have anti‐p155 autoantibody. One of 49 patients with lupus, and none of 89 others without myositis, had anti‐p155. Caucasian patients with anti‐p155 had a unique HLA risk factor, DQA1*0301 (odds ratio 5.4, corrected P = 0.004). In adults with anti‐p155, of several clinical features assessed only the frequency of V‐sign rash was increased, but patients with this antibody were clinically distinct from those with autoantibodies to aminoacyl–transfer RNA synthetases.

Conclusion

A newly recognized autoantibody, anti‐p155, is associated with DM and cancer‐associated DM, and is one of the most common autoantibodies in this condition, occurring as frequently in children as in adults. The clinical features and immunogenetics associated with anti‐p155 differ from those associated with antisynthetases.
Large‐scale gene expression profiling reveals major pathogenetic pathways of cartilage degeneration in osteoarthritis
Authors: Aigner Thomas , Fundel Katrin , Saas Joachim , Gebhard Pia M. , Haag Jochen , Weiss Tilo , Zien Alexander , Obermayr Franz , Zimmer Ralf , Bartnik Eckart
Published: October 2006

Objective

Despite many research efforts in recent decades, the major pathogenetic mechanisms of osteoarthritis (OA), including gene alterations occurring during OA cartilage degeneration, are poorly understood, and there is no disease‐modifying treatment approach. The present study was therefore initiated in order to identify differentially expressed disease‐related genes and potential therapeutic targets.

Methods

This investigation consisted of a large gene expression profiling study performed based on 78 normal and disease samples, using a custom‐made complementary DNA array covering >4,000 genes.

Results

Many differentially expressed genes were identified, including the expected up‐regulation of anabolic and catabolic matrix genes. In particular, the down‐regulation of important oxidative defense genes, i.e., the genes for superoxide dismutases 2 and 3 and glutathione peroxidase 3, was prominent. This indicates that continuous oxidative stress to the cells and the matrix is one major underlying pathogenetic mechanism in OA. Also, genes that are involved in the phenotypic stability of cells, a feature that is greatly reduced in OA cartilage, appeared to be suppressed.

Conclusion

Our findings provide a reference data set on gene alterations in OA cartilage and, importantly, indicate major mechanisms underlying central cell biologic alterations that occur during the OA disease process. These results identify molecular targets that can be further investigated in the search for therapeutic interventions.
Activation of nitric oxide signaling by the rheumatoid arthritis shared epitope
Authors: Ling Song , Lai Angela , Borschukova Olga , Pumpens Paul , Holoshitz Joseph
Published: October 2006

Objective

Susceptibility to rheumatoid arthritis (RA) is closely associated with HLA–DRB1 alleles encoding a shared epitope (SE) in positions 70–74 of the HLA–DRβ chain. The mechanistic basis for this association is unknown. Given the proposed pathogenic role of nitric oxide (NO) in RA, this study was undertaken to examine whether the SE can trigger NO signaling events.

Methods

The intracellular levels of NO were measured with the fluorescent NO probe 4,5‐diaminofluorescein diacetate and by the 2,3‐diaminonaphthalene method. NO synthase activity was determined by measuring the rate of conversion of radioactive arginine to citrulline. Levels of cGMP were measured with a commercial enzyme‐linked immunosorbent assay, and the cytolytic activity of T cells was measured using a standard 51Cr release assay.

Results

Lymphoblastoid B cell lines carrying SE‐positive HLA–DR alleles displayed a higher rate of spontaneous NO production compared with SE‐negative cells. L cell transfectants expressing SE‐positive DR molecules on their surface also generated higher levels of NO. Tetrameric HLA–DR molecules containing a DRβ‐chain encoded by the SE‐positive DRB1*0401 allele stimulated fibroblast cells to produce higher levels of NO compared with cells stimulated with a control HLA–DR tetramer. Multimeric hepatitis B core proteins engineered to express region 65–79 encoded by the DRB1*0401 allele, but not the same region encoded by the control allele DRB1*0402, stimulated NO production in fibroblasts. Similarly, synthetic 15‐mer peptides corresponding to the region 65–79 encoded by SE‐positive alleles triggered increased NO levels when incubated with class II major histocompatibility complex–negative cells. The signaling pathway was found to involve NO synthase activation, followed by increased production of cGMP. SE‐triggered increased NO levels inhibited cytolytic elimination of target cells.

Conclusion

The SE can trigger NO‐mediated signaling events in opposite cells, and may thereby contribute to RA pathogenesis.
NK026680, a novel suppressant of dendritic cell function, prevents the development of rapidly progressive glomerulonephritis and perinuclear antineutrophil cytoplasmic antibody in SCG/Kj mice
Authors: Saiga Kan , Tokunaka Kazuhiro , Ichimura Eiji , Toyoda Eriko , Abe Fuminori , Yoshida Minako , Furukawa Hiroshi , Nose Masato , Ono Masao
Published: October 2006

Objective

NK026680 is a newly identified type of immunosuppressive agent that inhibits dendritic cell (DC) functions and consequently reduces the mortality of mice with experimental acute graft‐versus‐host disease. This study was undertaken to evaluate NK026680 suppression of DC functions in preventing development of rapidly progressive glomerulonephritis (RPGN) and perinuclear antineutrophil cytoplasmic antibodies (pANCA) in SCG/Kj mice.

Methods

Oral administration of NK026680 to SCG/Kj mice began when mice were 8–10 weeks old, before the onset of disease, and continued for 56 days. The efficacy of NK026680 was evaluated using the mortality of mice, the results of urinalysis, histopathologic evaluation for glomerular injury, and immunofluorescence staining for the detection of immune complex (IC) deposition in glomeruli, and by assessing lymphadenopathy and measuring autoantibody titers.

Results

Oral administration of NK026680 at a dosage of 25 mg/kg once daily or 50 mg/kg once daily significantly suppressed 1) spontaneous mortality, 2) proteinuria and hematuria, 3) blood urea nitrogen levels, 4) glomerular damage characterized histopathologically, 5) IC deposition in glomeruli, 6) the development of pANCA and anti‐DNA antibodies, and 7) lymphadenopathy.

Conclusion

The newly identified DC inhibitor, NK026680, prevented the onset of RPGN, autoantibody production, and lymphadenopathy in SCG/Kj mice, suggesting a crucial role for DC function in these autoimmune phenotypes. NK026680 may be a potent immunosuppressive agent for the treatment of ANCA‐associated renovascular disorders.
Expansion of toll‐like receptor 9–expressing B cells in active systemic lupus erythematosus: Implications for the induction and maintenance of the autoimmune process
Authors: Papadimitraki Eva D. , Choulaki Christianna , Koutala Eleni , Bertsias George , Tsatsanis Christos , Gergianaki Irini , Raptopoulou Amalia , Kritikos Heraklis D. , Mamalaki Clio , Sidiropoulos Prodromos , Boumpas Dimitrios T.
Published: October 2006

Objective

Toll‐like receptors (TLRs) are pattern‐associated receptors in innate immunity that may be involved in the recognition of self antigens and the production of pathogenic autoantibodies. This study was undertaken to examine the expression and function of various TLRs in subpopulations of peripheral blood mononuclear cells (PBMCs) of patients with systemic lupus erythematosus (SLE).

Methods

The expression of TLRs in PBMCs from 50 SLE patients with active disease (SLE Disease Activity Index [SLEDAI] score ≥8; n = 26) or inactive disease (SLEDAI score <8; n = 24) and 20 healthy controls was studied by flow cytometry. TLR expression was assessed on various subpopulations of PBMCs (TLR‐2 and TLR‐4 by membrane staining; TLR‐3 and TLR‐9 by intracellular staining). TLR function was accessed by stimulating PBMCs with specific ligands.

Results

The proportion of B cells and monocytes expressing TLR‐9 was higher among patients with active SLE (mean ± SD 49.5 ± 24.4% and 30.7 ± 24.1%, respectively) than among patients with inactive disease (22.8 ± 19.6% and 14.3 ± 8.4%, respectively; P = 0.02 and P = 0.03). Among B cells, the proportion of plasma cells and memory B cells expressing TLR‐9 was increased in patients with active SLE. Increased percentages of TLR‐9–expressing B cells correlated with the presence of anti–double‐stranded DNA antibodies (P = 0.007). Treatment with serum from patients with active disease increased the percentage of TLR‐9–expressing plasma cells in serum from healthy controls. Enhanced induction of HLA–DR after TLR‐9 stimulation was documented in B cells from patients with active disease.

Conclusion

In patients with active SLE, the proportion of peripheral blood memory B cells and plasma cells expressing TLR‐9 is increased. Endogenous nucleic acids released during apoptotic cell death may stimulate B cells via TLR‐9 and contribute to SLE pathogenesis.
B cell depletion therapy in systemic lupus erythematosus: Effect on autoantibody and antimicrobial antibody profiles
Authors: Cambridge G. , Leandro M. J. , Teodorescu M. , Manson J. , Rahman A. , Isenberg D. A. , Edwards J. C.
Published: October 2006

Objective

Autoantibody production in patients with systemic lupus erythematosus (SLE) is associated with abnormalities of B cell function and phenotype. Clinical responses to B cell depletion therapy (BCDT), based on rituximab, are encouraging. Therefore, we undertook this study to investigate the effect of BCDT on antibody profiles.

Methods

Serial sera from 16 patients with active, refractory SLE were assayed for antinucleosome antibodies, anti–double‐stranded DNA (anti‐dsDNA), anti–extractable nuclear antigen, anti–tetanus toxoid, and antibodies to pneumococcal capsular polysaccharide for at least 1 year following BCDT. Anti‐dsDNA antibodies derived from the VH4.34 immunoglobulin germ line gene (9G4+) were also measured.

Results

All patients achieved peripheral B cell depletion and improved clinically for at least 3 months. Antinucleosome and anti‐dsDNA antibodies decreased to a mean ± SD of 64 ± 37% and 38 ± 33% of baseline values, respectively, by 6–8 months post‐BCDT. Levels of other autoantibodies and antimicrobial antibodies were generally unchanged. In the 9 of 16 patients who were still well at 1 year, anti‐dsDNA antibodies fell to 42 ± 36% of baseline values at 6–8 months and to 37 ± 33% at 10–14 months. In patients who had disease flares within 1 year of BCDT, levels of these antibodies decreased to 60 ± 40% and 83 ± 93% of baseline values at 6–8 months and at 10–14 months, respectively. Circulating anti‐dsDNA antibodies were positive for 9G4 expression in 4 of 6 patients tested, and flares in 2 of these patients were accompanied by rises in 9G4+ anti‐dsDNA antibodies.

Conclusion

These observations suggest that B cell clones committed to producing antinucleosome and anti‐dsDNA antibodies, including the VH4.34 subpopulation of anti‐dsDNA antibodies, have a relatively rapid turnover compared with B cell clones producing other antibodies. There was also a trend toward a greater and more sustained decrease in anti‐dsDNA antibodies in patients with clinical benefit lasting >1 year.
Simultaneous assessment of short‐term gastrointestinal benefits and cardiovascular risks of selective cyclooxygenase 2 inhibitors and nonselective nonsteroidal antiinflammatory drugs: An instrumental variable analysis
Authors: Schneeweiss Sebastian , Solomon Daniel H. , Wang Philip S. , Rassen Jeremy , Brookhart M. Alan
Published: October 2006

Objective

To simultaneously assess the short‐term reduction in risk of gastrointestinal (GI) complications and increase in risk of acute myocardial infarction (MI) by celecoxib compared with rofecoxib and several nonselective nonsteroidal antiinflammatory drugs (NSAIDs) using instrumental variable analysis.

Methods

A population of 49,711 Medicare beneficiaries ages 65 years and older who initiated nonselective NSAID or selective cyclooxygenase 2 inhibitor therapy between January 1, 1999, and December 31, 2002, was identified. The increase in risk of GI complications and MI within 180 days after initiation of NSAID (rofecoxib, diclofenac, ibuprofen, and naproxen compared with celecoxib) therapy was assessed using instrumental variable analysis.

Results

Compared with nonselective NSAIDs, celecoxib reduced the risk of GI complications by 1.4 per 100 users but increased the risk of MI by 0.3 per 100 users. Rofecoxib decreased GI complications by 1.1 per 100 users and increased the risk of MI by 0.3 per 100 users. Using celecoxib as the reference exposure showed an increase in the MI risk for rofecoxib (risk difference [RD] 1.40, 95% confidence interval [95% CI] −0.20, 3.01) and diclofenac (RD 6.07, 95% CI −0.02, 12.15). The RD for naproxen as well as its upper 95% CI was the lowest of all NSAIDs (RD −0.30, 95% CI −2.74, 2.14) and there was no significant difference in GI complication rates among all NSAIDs.

Conclusion

In this instrumental variable analysis, diclofenac and rofecoxib had the least favorable benefit–risk balance among NSAIDs in older adults.
Synthesis, Solution Thermodynamics, and X‐ray Study of CuII [12]Metallacrown‐4 with GABA Hydroxamic Acid: An Unprecedented Crystal Structure of a [12]MC‐4 with a γ‐Aminohydroxamate
Authors: Tegoni Matteo , Ferretti Luca , Sansone Francesco , Remelli Maurizio , Bertolasi Valerio , Dallavalle Francesco
Published: October 2006

The solution equilibria of γ‐aminobutanehydroxamic acid (GABAha) with H+ and Cu2+ were investigated by potentiometry, titration calorimetry, spectrophotometry, NMR spectroscopy, and ESI‐MS. The thermodynamic parameters of the CuII [12]metallacrown‐4 obtained for GABAha were compared with those of the corresponding complexes of (S)‐α‐Alaha and β‐Alaha. The stability (−ΔG0) sequence was β‐Alaha≫α‐Alaha>GABAha, whereas the order of formation enthalpies (−ΔH0) was β‐Alaha≫GABAha>α‐Alaha. These data were interpreted on the basis of the dimensions of the chelate rings and the planarity of the metallamacrocycles. The CuII [12]metallacrown‐4 ([12]MC‐4) complex of GABAha was isolated and its crystal structure, which is the first reported for a [12]MC‐4 of a γ‐aminohydroxamic acid, fully supports the structural features interpreted from the thermodynamic data.
Outcome of gastric cancer patients after successful gastrectomy
Authors: Rohatgi Pooja R. , Yao James C. , Hess Kenneth , Schnirer Isac , Rashid Asif , Mansfield Paul F. , Pisters Peter W. , Ajani Jaffer A.
Published: October 2006

BACKGROUND.

The effect of the location of disease recurrence after curative (R0) gastrectomy on patient survival has not been elucidated. The authors hypothesized that the location of recurrence would have a significant influence on survival.

METHODS.

Medical records of all patients who received treatment for gastric cancer at The University of Texas M. D. Anderson Cancer Center between 1985 and 1998 were reviewed. Patients who underwent R0 resection for gastric cancer and subsequently developed localized (anastomotic) recurrence (LR), lymph node (regional) recurrence (NR), or distant metastases (DM) were analyzed for overall survival (OS). All study factors were entered into a Cox proportional hazards model to provide multivariate hazard ratios. The model was adjusted for the effects of primary site of recurrence, histologic grade, patient age, and location of the primary tumor.

RESULTS.

This retrospective analysis included 227 consecutive patients. The median survival of patients who developed NR (11 months) was similar to that of patients who developed LR (10 months), but both groups had significantly longer median survival compared with patients who developed DM (7 months; log‐rank P = .03). Patients who had well differentiated or moderately differentiated tumors had a longer OS (11 months) than patients who had poorly differentiated tumors (8 months; log‐rank P = .02). In this cohort, location of the primary cancer and age at recurrence had no significant impact on OS.

CONCLUSIONS.

The data from this study suggested that, among patients who undergo R0 gastrectomy for gastric cancer, LR and NR versus DM should be considered a valid stratification factor for randomized trials based on significant differences in survival. Determining whether this stratification should apply to histologic differentiation will require further investigation in a larger multicenter cohort. Cancer 2006. © 2006 American Cancer Society.
Compartmental Modeling of the Fluorescence Anisotropy Decay of a Cylindrically Symmetric Brownian Rotor: Identifiability Analysis
Authors: Boens Noël , Novikov Eugene , Ameloot Marcel
Published: October 2006

We present the results of the deterministic identifiability analysis based on similarity transformation for models of one‐state excited‐state events of cylindrically symmetric rotors in isotropic environments undergoing rotational diffusion described by Brownian reorientation. Such an analysis on error‐free time‐resolved fluorescence (anisotropy) data can reveal whether the parameters of the considered model can be determined. The fluorescence δ‐response functions I||(t) and I⊥(t), for fluorescence polarized respectively parallel and perpendicular to the electric vector of linearly polarized excitation, are used to construct, in convenient matrix form, expressions of the sum S(t)=I||(t)+2 I⊥(t), the difference D(t)=I||(t)−I⊥(t), and the time‐resolved fluorescence anisotropy r(t)=D(t)/S(t). The identifiability analysis of r(t) demonstrates that the rotational diffusion coefficients D|| and D⊥ for rotation respectively about and perpendicular to the symmetry axis can be uniquely resolved. However, the polar and azimuthal angles defining the absorption and emission transition moments in the molecular reference frame are not individually identifiable. Nevertheless, the difference between the polar angles of these transition moments is uniquely determined.
Combinatorial expression patterns of heparan sulfate sulfotransferases in zebrafish: II. The 6‐O‐sulfotransferase family
Authors: Cadwallader Adam B. , Yost H. Joseph
Published: October 2006

Heparan sulfate (HS) is an unbranched chain of repetitive disaccharides, which specifically binds ligands when attached to the cell surface or secreted extracellularly. HS chains contain sulfated domains termed the HS fine structure, which gives HS specific binding affinities for extracellular ligands. HS 6‐O‐sulfotransferases (6‐OST) catalyze the transfer of sulfate groups to the 6‐O position of glucosamine residues of HS. We report here the characterization and developmental expression analysis of the 6‐OST gene family in the zebrafish. The zebrafish 6‐OST gene family consists of four conserved vertebrate orthologues, including a gene duplication specific to zebrafish. We examined the mRNA expression patterns in several tissues/organs throughout early zebrafish development, including early cleavage stages, eyes, somites, brain, internal organ primordial, and pectoral fin development. Members of the 6‐OST gene family have spatially and temporally distinct restricted expression, suggesting in vivo functional differences exist between members of this family. Developmental Dynamics 235:3432–3437, 2006. © 2006 Wiley‐Liss, Inc.