bluuebunny/crossref_metadata_2025 huggingface dataset:
A systematic review of the evidence for hip surveillance in children with cerebral palsy
Authors: Gordon G. S. , Simkiss D. E.
Published: October 2006

We reviewed the evidence for hip surveillance in children with cerebral palsy from the published literature.

Publications were identified using the Cochrane controlled trials register, the MEDLINE, EMBASE and CINAHL databases and by hand searching key journals and their references. Studies were included if they reported the frequency, associated risk factors or surveillance measures undertaken to identify subluxation or dislocation of the hip in children with cerebral palsy. Assessment of the quality of the methodology was undertaken independently by two researchers.

Four studies described the natural history, incidence and risk factors for dislocation of the hip. Two reported their surveillance results. Approximately 60% of children who were not walking by five years of age were likely to develop subluxation of the hip, with the greatest risk in those with severe neurological involvement. The introduction of surveillance programmes allowed earlier identification of subluxation and reduced the need for surgery on dislocated hips.

Surveillance can identify children most at risk of subluxation using radiological methods which are widely available.
@ TOG
Authors: Edey Katharine , Barnfield Sonia , Jenkins Julian
Published: October 2006

In this issue of TOG we review MRCOG Part 2 related websites. Access to online Multiple Choice Questions (MCQs), Extended Matching Questions (EMQs) and essays, along with tutorials, can be a very useful adjunct to the revision process.
Electroplating and calcium carbonate sludges as binding material for sludge solidification
Authors: Yang Gordon C. C. , Kao Kai‐Lun
Published: October 2006

Resource recycling and wastes treating wastes are the basic concepts of this study which uses a heat‐treated mixture of an electroplating sludge and a calcium carbonate sludge as a binder for sludge solidification. The heat‐treated mixture was prepared by mixing the above two industrial wastes at 1 000°C for 4 hours. It was then used to partially replace (10, 20, and 40 wt% replacement) Portland cement for solidification of the original, hazardous electroplating sludge. The heat‐treated waste mixture was found to have an excellent binding capability. Moreover, the monoliths solidified by this binder system have exhibited outstanding physicochemical properties, including unconfined compressive strength, TCLP leaching toxicity, acid neutralization capacity, resistance to repetitive leaching by a synthetic acid rain, resistance to freezing‐thawing cycling, and resistance to wetting‐drying cycling.
Estimating the effects of misleading information on witness accuracy: can experts tell jurors something they don't already know?
Authors: McAuliff Bradley D. , Kovera Margaret Bull
Published: October 2006

This study investigated potential differences between expert and lay knowledge of factors influencing witness suggestibility. Expert psychologists (N = 58), jurors (N = 157), and jury‐eligible undergraduates (N = 220) estimated the effects of misleading information on witness accuracy for three age groups in various conditions. Respondents possessed similar knowledge of age‐related trends in suggestibility, the positive effects of a pre‐misinformation warning, and the negative influence of longer delays between the event/misinformation and event/final memory test. Compared to experts, laypeople underestimated the size of suggestibility differences between age groups and lacked knowledge about how event detail centrality, witness participation, and source prestige can increase witness suggestibility. Laypeople rated themselves as being largely unfamiliar with witness suggestibility research and thought that expert testimony would be beneficial. These data shed light on the potential helpfulness of expert testimony in cases involving witness suggestibility. Copyright © 2006 John Wiley & Sons, Ltd.
Kaskadenreaktionen in der Totalsynthese
Authors: Nicolaou K. C. , Edmonds David J. , Bulger Paul G.
Published: October 2006

Die Entwicklung und Umsetzung von Kaskadenreaktionen hat zu beachtlichen neuartigen, eleganten und effizienten Synthesestrategien geführt. Als besonders anspruchsvoll erwies sich die Anwendung von Kaskadenreaktionen in der Naturstoffsynthese, doch gerade hier winken verblüffende und zugleich aufschlussreiche Ergebnisse als Belohnung. In diesem Aufsatz werden ausgewählte Kaskadenreaktionen in der Totalsynthese erläutert, wobei neuere Anwendungen besonders hervorgehoben werden. Die erörterten Beispiele sollen die Leistungsfähigkeit dieser Prozesse beim Aufbau von komplexen Molekülstrukturen veranschaulichen und ihr Potenzial für zukünftige chemische Synthesen verdeutlichen.
Cascade Reactions in Total Synthesis
Authors: Nicolaou K. C. , Edmonds David J. , Bulger Paul G.
Published: October 2006

The design and implementation of cascade reactions is a challenging facet of organic chemistry, yet one that can impart striking novelty, elegance, and efficiency to synthetic strategies. The application of cascade reactions to natural products synthesis represents a particularly demanding task, but the results can be both stunning and instructive. This Review highlights selected examples of cascade reactions in total synthesis, with particular emphasis on recent applications therein. The examples discussed herein illustrate the power of these processes in the construction of complex molecules and underscore their future potential in chemical synthesis.
Role of lignin filler in stabilization of natural rubber–based composites
Authors: Košíková B. , Gregorová A. , Osvald A. , Krajčovičová J.
Published: October 2006

The stabilizing effect of a natural filler, sulfur‐free lignin, on the thermal degradation of natural rubber (NR) was examined. Lignin was incorporated into NR in amounts of 10–30 phr (parts per hundred parts of rubber). It was shown that the lignin preparation used improved the physicomechanical properties of the rubber vulcanizates. Thermogravimetric analysis and differential scanning calorimetry were used to study the thermal degradation of unfilled and lignin‐filled vulcanized natural rubber. Measurements were carried out under atmospheric conditions. It was revealed that lignin used as filler increased the resistance of NR vulcanizates to thermooxidative degradation in air. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 1226–1231, 2007
Synthesis and characterization of cholesteric thermotropic liquid crystalline polyesters
Authors: Jadhav Sushilkumar A. , Chougule Rahul R. , Shinde Yogesh A. , Chavan N. N.
Published: October 2006

Cholesteric liquid crystalline polyesters were successfully synthesized from isosorbide, methyl hydroquinone, and isophthaloyl chloride. Homo/copolyesters were synthesized by the solution polycondensation method, for which a mild organic base such as pyridine was employed. Inherent viscosities of polyesters P‐3–P‐5 were in the range of 0.31–0.39 dL/g at 25°C in chloroform, and polyesters P‐1 and P‐2 were insoluble in chloroform. Homo/copolyesters based on isosorbide, methyl hydroquinone, and isophthalic acid had thermal stability at more than 300°C on the basis of 10% weight loss. The thermotropic liquid crystalline properties were examined by differential scanning calorimetry and polarizing optical microscopy. Wide‐angle X‐ray diffraction study demonstrated that polyesters P‐1, P‐2, and P‐3 were semicrystalline, whereas the degree of crystallinity of polyesters P‐4 and P‐5 was less than 5%. Copolyester P‐4 showed formation of a yellow iridescent streak at 209°C on heating and development of a Grandjean texture at 270°C on heating. These are typical textures of the cholesteric liquid crystalline phase. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 1232–1237, 2007
New approach for the preparation of nanoporous polyorganosilicate low‐k films
Authors: Xi Kai , Guo Rui , Weng Yangyang , He Hui , Shao Qiang , Cai Jie , Chen Qingmin , Yu Xuehai , Jia Xudong
Published: October 2006

The distribution of pores and the mechanical properties of materials are the key factors in preparing satisfactory low‐k films. In the present study, a kind of silsesquioxane‐polyethylene glycol (SSQ‐PEG) was synthesized and used as a template to make the distribution of pores more even in the low‐k films. The crosslinking density of films could be adjusted by the sol‐gel of tetramethoxysilane/dimethoxydimethylsilane with various proportions. The porosity of films could also be adjusted with different proportions of pendant PEG chains introduced. A dielectric constant as low as 2.1 had been achieved for nanoporous polyorganosilicate films with good tenacity. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 1238–1243, 2007
Effects of thermal aging on fatigue of carbon black–reinforced EPDM rubber
Authors: Chou Hsoung‐Wei , Huang Jong‐Shin , Lin Shih‐Ting
Published: October 2006

Deterioration of the parameters measuring the fatigue of rubber compounds as a result of thermal aging was investigated. The energy to break, tear strength, fatigue life, and fatigue crack propagation rate of EPDM rubber compounds reinforced with three different types of carbon black before and after different periods of thermal aging were measured and compared through a series of static and cyclic loading tests. The experimental results indicated that the fatigue resistance of EPDM rubber compounds with different types of carbon black was consistently reduced because of changes in the molecular structure and crosslink density as a result of thermal aging. Meanwhile, the intrinsic flaws of carbon black–reinforced EPDM rubber compounds after 6 months of thermal aging were smaller, regardless of the type of carbon black. Therefore, the effects of thermal aging on the fatigue of rubber compounds are significant and should be taken into account in designing rubber components. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 1244–1251, 2007
Analysis of network structure formed in styrene–butadiene rubber cured with sulfur/TBBS system
Authors: Marzocca A. J. , Mansilla M. A.
Published: October 2006

Several styrene–butadiene rubber (SBR) compounds were prepared with different cure systems based on sulfur and TBBS (N‐t‐butyl‐2‐benzothiazole sulfenamide), varying the amount of sulfur and accelerator between 0.5 and 2.5 phr in the formulation. Torque curves, measured with a moving die rheometer at temperatures at 433 K, were used to characterize the vulcanization. The time to achieve the maximum torque, t100%, was evaluated for each sample, and this time was set to vulcanize sheets at 433 K. The density and type of elastically active crosslinks of each cured sample were evaluated by means of swelling measurements and were related to the vulcanizing system. Finally, the rheometer data were analyzed considering the network structure formed during vulcanization. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 1105–1112, 2007
Solid‐state polymerization of poly(ethylene 2,6‐naphthalate)
Authors: Duh Ben
Published: October 2006

The solid‐state polymerization (SSP) of poly (ethylene 2,6‐naphthalate) (PEN) was studied and compared with that of poly(ethylene terephthalate) (PET). The SSP of PEN, like that of PET, could be satisfactorily described with a modified second‐order kinetic model, which was based on the assumptions that part of the end groups were inactive during SSP and that the overall SSP followed second‐order kinetics with respect to the active end‐group concentration. The proposed rate equation fit the data of the SSP of PEN quite well under various conditions. PEN prepolymers in pellet and cube forms with intrinsic viscosities (IVs) ranging from 0.375 to 0.515 dL/g, various particle sizes, and various carboxyl concentrations were solid‐state polymerized at temperatures ranging from 240 to 260°C to study the effects of various factors. The SSP data obtained in this study could be readily applied to the design of commercial PEN SSP processes. Because PEN and PET share the same SSP mechanism, in general, the SSP behaviors of PEN are similar to those of PET. Thus, the SSP rate of PEN increased with increasing temperature, increasing prepolymer IV, and decreasing prepolymer particle size. However, because of the much higher barrier properties of PEN, the prepolymer particle size and carboxyl concentration had much greater effects on the SSP of PEN than on the SSP of PET. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 1075–1084, 2007
Miscibility behavior of blend of polyesteramides of linseed oil and dehydrated castor oil with poly(methacrylic acid)
Authors: Ashraf S. M. , Ahmad Sharif , Riaz Ufana , Alam Manawwer , Sharma H. O.
Published: October 2006

Blending of two polymers in solution is a simple and cost‐effective technique to improve upon the physical and mechanical properties of the component polymers through synergism. To obtain maximum synergy in their properties, the component polymers should be miscible with each other on molecular scale. Polymer blends of complex physicomechanical properties are being actively investigated. Poly(methacrylic acid) (PMAA), a commercial polymer, yields transparent, hard, brittle, and water‐sensitive films. It has been blended with natural polymers like dextran, collagen, and gelatin to obtain films with improved physical and mechanical characteristics. Polyesteramides, which are easily synthesized from vegetable seeds oil, a sustainable resource, have found application in surface coatings. These oligomeric products do not make free standing films in the ambient condition. The polyesteramides from vegetable seeds oil can be used to obtain blend with PMMA of improved mechanical and water absorption properties. In this study, linseed oil polyesteramide (LOPEA) and dehydrated castor oil polyesteramide (DCPEA), the source oils with different unsaturation in their fatty acid chains, were blended with PMAA through mixing in solution in the ratio DCPEA/LOPEA: PMAA as 80/20, 70/30, 60/40, 50/50, 40/60, 30/70, and 20/80. In the first instance, the miscibility of the two components was investigated in solution by viscosity and ultrasonic measurements and in solid phase through differential scanning calorimetry (DSC) and scanning electron microscopy (SEM). Moisture absorption by the blend was also studied. DCPEA and LOPEA show immiscibility with PMAA in solution phase while LOPEA with more unsaturation in the fatty acid chain of the oil was found more immiscible than DCPEA. DCPEA shows a narrow miscibility window in the solid phase while LOPEA was found immiscible with PMAA in the solid phase too. Uptake of moisture was found to be markedly reduced in the blends of DCPEA/LOPEA with PMAA. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 1367–1374, 2007:
Human cranial anatomy and the differential preservation of population history and climate signatures
Authors: Harvati Katerina , Weaver Timothy D.
Published: October 2006

Cranial morphology is widely used to reconstruct evolutionary relationships, but its reliability in reflecting phylogeny and population history has been questioned. Some cranial regions, particularly the face and neurocranium, are believed to be influenced by the environment and prone to convergence. Others, such as the temporal bone, are thought to reflect more accurately phylogenetic relationships. Direct testing of these hypotheses was not possible until the advent of large genetic data sets. The few relevant studies in human populations have had intriguing but possibly conflicting results, probably partly due to methodological differences and to the small numbers of populations used. Here we use three‐dimensional (3D) geometric morphometrics methods to test explicitly the ability of cranial shape, size, and relative position/orientation of cranial regions to track population history and climate. Morphological distances among 13 recent human populations were calculated from four 3D landmark data sets, respectively reflecting facial, neurocranial, and temporal bone shape; shape and relative position; overall cranial shape; and centroid sizes. These distances were compared to neutral genetic and climatic distances among the same, or closely matched, populations. Results indicate that neurocranial and temporal bone shape track neutral genetic distances, while facial shape reflects climate; centroid size shows a weak association with climatic variables; and relative position/orientation of cranial regions does not appear correlated with any of these factors. Because different cranial regions preserve population history and climate signatures differentially, caution is suggested when using cranial anatomy for phylogenetic reconstruction. Anat Rec Part A, 2006. © 2006 Wiley‐Liss, Inc.
Risedronate decreases biochemical markers of cartilage degradation but does not decrease symptoms or slow radiographic progression in patients with medial compartment osteoarthritis of the knee: Results of the two‐year multinational knee osteoarthritis structural arthritis study
Authors: Bingham Clifton O. , Buckland‐Wright J. Chris , Garnero Patrick , Cohen Stanley B. , Dougados Maxime , Adami Silvano , Clauw Daniel J. , Spector Timothy D. , Pelletier Jean‐Pierre , Raynauld Jean‐Pierre , Strand Vibeke , Simon Lee S. , Meyer Joan M. , Cline Gary A. , Beary John F.
Published: October 2006

Objective

Bisphosphonates have slowed the progression of osteoarthritis (OA) in animal models and have decreased pain in states of high bone turnover. The Knee OA Structural Arthritis (KOSTAR) study, which is the largest study to date investigating a potential structure‐modifying OA drug, tested the efficacy of risedronate in providing symptom relief and slowing disease progression in patients with knee OA.

Methods

The study group comprised 2,483 patients with medial compartment knee OA and 2–4 mm of joint space width (JSW), as determined using fluoroscopically positioned, semiflexed‐view radiography. Patients were enrolled in 2 parallel 2‐year studies in North America and the European Union. These studies evaluated the efficacy of risedronate at dosages of 5 mg/day, 15 mg/day, 35 mg/week (in Europe), and 50 mg/week (in North America) compared with placebo in reducing signs and symptoms, as measured by the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index and patient global assessment (PGA) scores, and in slowing radiographic progression.

Results

A reduction of ∼20% in signs and symptoms, as measured by WOMAC subscales and PGA scores, was observed in all groups, with no treatment effect of risedronate demonstrated. Risedronate did not significantly reduce radiographic progression as measured by decreased JSW or using a dichotomous definition of progression (joint space loss of ≥0.6 mm). Thirteen percent of patients receiving placebo demonstrated significant disease progression over 2 years. A dose‐dependent reduction in the level of C‐terminal crosslinking telopeptide of type II collagen, a cartilage degradation marker associated with progressive OA, was seen in patients who received risedronate. No increase in the number of adverse events was demonstrated for risedronate compared with placebo.

Conclusion

Although risedronate (compared with placebo) did not improve signs or symptoms of OA, nor did it alter progression of OA, a reduction in the level of a marker of cartilage degradation was observed. A sustained clinically relevant improvement in signs and symptoms was observed in all treatment and placebo groups.
Antiviral therapy for hepatitis C virus–associated mixed cryoglobulinemia vasculitis: A long‐term followup study
Authors: Saadoun David , Resche‐Rigon Mathieu , Thibault Vincent , Piette Jean‐Charles , Cacoub Patrice
Published: October 2006

Objective

To evaluate the long‐term efficacy of anti–hepatitis C virus (HCV) therapy in patients with HCV‐associated mixed cryoglobulinemia (HCV‐MC) vasculitis and to assess the factors associated with clinical remission of MC.

Methods

This was a single‐center study of 72 consecutive patients who received treatment with IFN alfa‐2b (3 million IU 3 times a week; n = 32 patients) or PEGylated IFN alfa‐2b (PEG–IFN alfa‐2b) (1.5 μg/kg/week; n = 40 patients), both in combination with oral ribavirin (600–1,200 mg/day), for at least 6 months. Logistic regression was used to assess factors associated with clinical remission of MC.

Results

The mean ± SD duration of followup after discontinuation of antiviral therapy was 39.7 ± 24.4 months. Eight deaths (11.1% of patients) occurred during the study, primarily as a result of cardiovascular disease, liver disease, or infection. A complete clinical response of the MC occurred in 45 patients (62.5%), a sustained virologic response occurred in 58.3%, and cryoglobulins cleared in 45.8%. Compared with patients treated with IFN alfa‐2b plus ribavirin, those receiving PEG–IFN alfa‐2b plus ribavirin had a higher sustained clinical (67.5% versus 56.3%), virologic (62.5% versus 53.1%), and immunologic (57.5% versus 31.3%) response, regardless of HCV genotype and viral load. In multivariate analyses, an early virologic response (odds ratio 3.53 [95% confidence interval 1.18–10.59]) was independently associated with a complete clinical response of MC. A glomerular filtration rate ≤70 ml/minute (odds ratio 0.18 [95% confidence interval 0.05–0.67]) was negatively associated with a complete clinical response of MC.

Conclusion

PEG–IFN alfa‐2b plus ribavirin should be considered as induction therapy for HCV‐MC vasculitis. An early virologic response and the absence of renal insufficiency are the key factors in the clinical response.
RhoA‐mediated, tumor necrosis factor α–induced activation of NF‐κB in rheumatoid synoviocytes: Inhibitory effect of simvastatin
Authors: Xu Hanshi , Liu Peng , Liang Liuqin , Danesh Farhad R. , Yang Xiuyan , Ye Yijin , Zhan Zhongping , Yu Xueqing , Peng Hui , Sun Lin
Published: October 2006

Objective

Increasing evidence indicates that RhoA may play a central role in the inflammatory response. This study was conducted to examine the role of RhoA in mediating the activation of NF‐κB in tumor necrosis factor α (TNFα)–stimulated rheumatoid synoviocytes, and to evaluate the modulatory effects of statins on the TNFα‐induced activation of RhoA and NF‐κB and the secretion of proinflammatory cytokines by rheumatoid synoviocytes.

Methods

Rheumatoid synoviocytes obtained from patients with active rheumatoid arthritis were stimulated with TNFα and incubated with simvastatin (SMV) (1 μM). RhoA activity was assessed by a pull‐down assay. NF‐κB DNA binding activity and nuclear translocation of NF‐κB were measured by a sensitive multiwell colorimetric assay and confocal fluorescence microscopy, respectively.

Results

TNFα stimulation elicited a robust increase in RhoA activity in a dose‐dependent manner, and SMV mitigated this increase. TNFα also hastened NF‐κB nuclear translocation of subunit p65 and increased DNA binding activity, luciferase reporter gene expression, degradation of IκB, and secretion of interleukin‐1β (IL‐1β) and IL‐6. SMV prevented the increase in NF‐κB activation and rise in IL‐1β and IL‐6 levels induced by TNFα, whereas mevalonate and geranylgeranyl pyrophosphate reversed the inhibitory effects of SMV on activation of NF‐κB and RhoA. Furthermore, cotransfection with a dominant‐negative mutant of RhoA demonstrated that the TNFα‐induced signaling pathway involved sequential activation of RhoA, leading to NF‐κB activation and, ultimately, to secretion of cytokines.

Conclusion

This study identifies RhoA as the key regulator of TNFα‐induced NF‐κB activation, which ultimately results in the secretion of proinflammatory cytokines in rheumatoid synoviocytes. The findings provide a new rationale for the antiinflammatory effects of statins in inflammatory arthritis.
Glycan analysis of monoclonal antibodies secreted in deposition disorders indicates that subsets of plasma cells differentially process IgG glycans
Authors: Omtvedt Lone A. , Royle Louise , Husby Gunnar , Sletten Knut , Radcliffe Catherine M. , Harvey David J. , Dwek Raymond A. , Rudd Pauline M.
Published: October 2006

Objective

To compare the glycosylation of polyclonal serum IgG heavy chains in a patient with rheumatoid arthritis (RA) with that of monoclonal serum IgG heavy chains in the same patient during an episode of heavy‐chain deposition disease (HCDD), to establish whether glycosylation processing is specific for subsets of B cells.

Methods

Serum IgG was purified using a HiTrap protein G column. Immunoglobulins were run on sodium dodecyl sulfate–polyacrylamide gel electrophoresis gels, and IgG glycans were isolated from gel bands and fluorescently labeled. Glycans were analyzed by normal‐phase high‐performance liquid chromatography and by liquid chromatography–electrospray ionization–mass spectrometry.

Results

The glycosylation of serum immunoglobulins from a patient with seronegative RA and HCDD was analyzed. The predominant immunoglobulin was a truncated glycosylated γ3 heavy chain, and a small amount of polyclonal IgG was also present. The glycan profile showed that the monoclonal γ3 heavy chain contained fully galactosylated biantennary glycans with significantly less fucose but more sialic acid than in IgG3 from healthy controls. In contrast, the polyclonal IgG showed an RA‐like profile, with a predominance of fucosylated biantennary glycans and low levels of galactosylation. The glycan profile of serum IgG obtained from the same patient during disease remission resembled a typical RA profile.

Conclusion

These data indicate that different types of B cells process a particular set of IgG glycoforms.
Impaired skeletal development in interleukin‐6–transgenic mice: A model for the impact of chronic inflammation on the growing skeletal system
Authors: De Benedetti Fabrizio , Rucci Nadia , Del Fattore Andrea , Peruzzi Barbara , Paro Rita , Longo Maurizio , Vivarelli Marina , Muratori Flaminia , Berni Silvia , Ballanti Paola , Ferrari Serge , Teti Anna
Published: October 2006

Objective

To identify the mediator responsible for the impact of chronic inflammation on skeletal development in children (bone loss, defective peak bone mass accrual, stunted growth), we evaluated the effects of chronic interleukin‐6 (IL‐6) overexpression on the skeletons of growing prepubertal mice.

Methods

We studied IL‐6–transgenic mice that had high circulating IL‐6 levels since birth. Trabecular and cortical bone structure were analyzed by microcomputed tomography. Epiphyseal ossification, growth plates, and calvariae were studied by histology/histomorphometry. Osteoclastogenesis, osteoblast function/differentiation, and the effects of IL‐6 on bone cells were studied in vitro. Osteoblast gene expression was evaluated by reverse transcriptase–polymerase chain reaction. The mineral apposition rate was evaluated dynamically in cortical bone by in vivo double fluorescence labeling.

Results

In prepubertal IL‐6–transgenic mice, we observed osteopenia, with severe alterations in cortical and trabecular bone microarchitecture, as well as uncoupling of bone formation from resorption, with decreased osteoblast and increased osteoclast number and activity. Increased osteoclastogenesis and reduced osteoblast activity, secondary to decreased precursor proliferation and osteoblast function, were present. IL‐6–transgenic mice also showed impaired development of growth plates and epiphyseal ossification centers. Intramembranous and endochondral ossification and the mineral apposition rate were markedly affected, showing the presence of defective ossification.

Conclusion

Chronic overexpression of IL‐6 alone induces a skeletal phenotype closely resembling growth and skeletal abnormalities observed in children with chronic inflammatory diseases, pointing to IL‐6 as a pivotal mediator of the impact of chronic inflammation on postnatal skeletal development. We hypothesize that IL‐6–modifying drugs may reduce skeletal defects and prevent the growth retardation associated with these diseases.
Efficacy and mechanism of action of turmeric supplements in the treatment of experimental arthritis
Authors: Funk Janet L. , Frye Jennifer B. , Oyarzo Janice N. , Kuscuoglu Nesrin , Wilson Jonathan , McCaffrey Gwen , Stafford Gregory , Chen Guanjie , Lantz R. Clark , Jolad Shivanand D. , Sólyom Aniko M. , Kiela Pawel R. , Timmermann Barbara N.
Published: October 2006

Objective

Scientific evidence is lacking for the antiarthritic efficacy of turmeric dietary supplements that are being promoted for arthritis treatment. Therefore, we undertook studies to determine the antiarthritic efficacy and mechanism of action of a well‐characterized turmeric extract using an animal model of rheumatoid arthritis (RA).

Methods

The composition of commercial turmeric dietary supplements was determined by high‐performance liquid chromatography. A curcuminoid‐containing turmeric extract similar in composition to these supplements was isolated and administered intraperitoneally to female Lewis rats prior to or after the onset of streptococcal cell wall–induced arthritis. Efficacy in preventing joint swelling and destruction was determined clinically, histologically, and by measurement of bone mineral density. Mechanism of action was elucidated by analysis of turmeric's effect on articular transcription factor activation, microarray analysis of articular gene expression, and verification of the physiologic effects of alterations in gene expression.

Results

A turmeric fraction depleted of essential oils profoundly inhibited joint inflammation and periarticular joint destruction in a dose‐dependent manner. In vivo treatment prevented local activation of NF‐κB and the subsequent expression of NF‐κB–regulated genes mediating joint inflammation and destruction, including chemokines, cyclooxygenase 2, and RANKL. Consistent with these findings, inflammatory cell influx, joint levels of prostaglandin E2, and periarticular osteoclast formation were inhibited by turmeric extract treatment.

Conclusion

These translational studies demonstrate in vivo efficacy and identify a mechanism of action for a well‐characterized turmeric extract that supports further clinical evaluation of turmeric dietary supplements in the treatment of RA.
Hepatocyte growth factor and transforming growth factor β1 ratio at baseline can predict early response to cyclophosphamide in systemic lupus erythematosus nephritis
Authors: Capuano Anna , Costanzi Stefano , Peluso Giusy , Zannoni Gianfranco , Vellone Valerio Gaetano , Gremese Elisa , Zoli Angelo , Scott Cathryn , Beltrami Carlo Alberto , Romano Giulio , Ferraccioli Gianfranco
Published: October 2006

Objective

To determine whether the ratio of hepatocyte growth factor (HGF) to transforming growth factor β1 (TGFβ1) in systemic lupus erythematosus (SLE) nephritis could be a prognostic factor for response to therapy with cyclophosphamide (CYC) and steroids at 6 months, and to examine whether the molecular ratio of HGF to TGFβ1 correlates with the activity index (AI) and chronicity index (CI) and has predictive value for remission at the sixth month.

Methods

Thirty‐six SLE patients with new‐onset nephritis, 25 of whom were treated with CYC and steroids, entered into a prospective observational cohort trial at a tertiary university referral center. Renal biopsy findings and clinical parameters were recorded for all patients. Histopathologic, clinical, and immunohistochemical data at baseline served to define the predictive value for the outcome at 6 months.

Results

AI and CI at baseline did not distinguish patients who had achieved remission from those who had not achieved remission after receiving CYC plus steroids. HGF and TGFβ1 were expressed in the tubuli, not in the glomeruli. The CI correlated directly with the TGFβ1 extension score (TGFβ1‐ES) (r = 0.43, P = 0.008), but correlated indirectly with the HGF intensity score (HGF‐IS) (r = −0.39, P = 0.02) and the HGF‐ES (r = −0.45, P = 0.006). An HGF‐ES:TGFβ1‐ES ratio of ≥1 at baseline distinguished patients who had achieved remission from those who had not achieved remission, with a predictive value of 94%.

Conclusion

These findings indicate that baseline expression of renal HGF and TGFβ1 predicts short‐term renal outcome after therapy with CYC and steroids.
Amyloid contained in the knee joint meniscus is formed from apolipoprotein A‐I
Authors: Solomon Alan , Murphy Charles L. , Kestler Daniel , Coriu Daniel , Weiss Deborah T. , Makovitzky Josef , Westermark Per
Published: October 2006

Objective

To determine the chemical nature of amyloid deposits found in knee joint menisci.

Methods

Amyloid was extracted from the menisci of 3 adults who underwent knee joint replacement surgery. The primary structural features of the purified proteins were determined by sequential Edman degradation and tandem mass spectrometry (MS/MS). Tissue specimens were also subjected to in situ hybridization analysis, as well as complementary DNA cloning by reverse transcriptase–polymerase chain reaction (RT‐PCR). Additionally, specimens from these 3 patients, as well as other patients with amyloid in the knee joint menisci, were examined immunohistochemically.

Results

Amino acid sequence and MS/MS analyses of the extracts revealed the presence of 60–77‐residue components identical to the N‐terminal portion of apolipoprotein A‐I (Apo A‐I). The Apo A‐I nature of the amyloid was confirmed by the demonstration that the green birefringent congophilic deposits in the 7 meniscus samples were recognized by an anti‐human Apo A‐I antibody. That the meniscus itself was the source of the amyloidogenic protein was evidenced through Southern blot analysis, in which an Apo A‐I product was generated by RT‐PCR from synovial tissue, and further, by the demonstration that the cytoplasm of chondrocytes reacted with the specific Apo A‐I probe used for in situ hybridization and was immunostained by the anti–Apo A‐I antiserum.

Conclusion

Amyloid in the knee joint menisci is formed from Apo A‐I that is produced by chondrocytes within the meniscal cartilage. This entity represents yet another localized form of amyloidosis associated with the aging process and may be of pathophysiologic import.
The effect of O2 tension on pH homeostasis in equine articular chondrocytes
Authors: Milner P. I. , Fairfax T. P. A. , Browning J. A. , Wilkins R. J. , Gibson J. S.
Published: October 2006

Objective

To determine the effects of varying O2 on pH homeostasis, based on the hypothesis that the function of articular chondrocytes is best understood at realistic O2 tensions.

Methods

Cartilage from equine metacarpophalangeal/tarsophalangeal joints was digested with collagenase to isolate chondrocytes, and then loaded with the pH‐sensitive fluorophore 2′,7′‐bis‐2‐(carboxyethyl)‐5(6)‐carboxylfluorescein. The radioisotope22Na+ was used to determine the kinetics of Na+/H+ exchange (NHE) and the activity of the Na+/K+ pump, and ATP levels were assessed with luciferin assays. Levels of reactive oxygen species (ROS) were determined using 2′,7′‐dichlorofluorescein diacetate.

Results

The pH homeostasis was unaffected when comparing tissue maintained at 20% O2 (the level in water‐saturated air at 37°C) with that at 5% O2 (which approximates the normal level in healthy cartilage); however, an O2 tension of <5% caused a fall in intracellular pH (pHi) and slowed pHi recovery following acidification, an effect mediated via inhibition of NHE activity (likely through acid extrusion by NHE isoform 1). The Na+/K+ pump activity and intracellular ATP concentration were unaffected by hypoxia, but the levels of ROS were reduced. Hypoxic inhibition of NHE activity and the reduction in ROS levels were reversed by treatment with H2O2, Co2+, or antimycin A. Treatment with calyculin A also prevented hypoxic inhibition of NHE activity.

Conclusion

The ability of articular chondrocytes to carry out pH homeostasis is compromised when O2 tensions fall below those normally experienced, via inhibition of NHE. The putative signal is a reduction in levels of ROS derived from mitochondria, acting via altered protein phosphorylation. This effect is relevant to both physiologic and pathologic states of lowered O2, such as in chronic inflammation.
Occupational silica and solvent exposures and risk of systemic lupus erythematosus in urban women
Authors: Finckh Axel , Cooper Glinda S. , Chibnik Lori B. , Costenbader Karen H. , Watts Julie , Pankey Helen , Fraser Patricia A. , Karlson Elizabeth W.
Published: October 2006

Objective

To assess the risk of systemic lupus erythematosus (SLE) associated with occupational exposure to silica dust and organic solvents in an urban population.

Methods

Women with SLE were identified through both community screening and hospital databases in 4 predominantly African American neighborhoods in Boston. Female control patients were volunteers from the same communities and were screened for the absence of connective tissue disease. Demographic factors, smoking history, and a detailed occupational history, including exposures to specific chemicals, were obtained by in‐person interviews. The exposure assessment was based on independent evaluation of the occupational history by 2 reviewers who were blinded to each subject's disease status. The risks associated with exposure to silica and solvents were analyzed using multivariate conditional logistic regression models, adjusted for potential confounders.

Results

Ninety‐five patients and 191 age‐ and race‐matched controls were included in this analysis. Exposure to silica for longer than 1 year was associated with SLE (odds ratio [OR] 4.3, 95% confidence interval [95% CI] 1.7–11.2). An exposure‐response effect was seen for longer duration of exposures to silica (P for trend = 0.01). The association between occupational exposure to organic solvents and SLE was not statistically significant (OR 1.04, 95% CI 0.34–3.2).

Conclusion

Silica exposure from a variety of industrial occupations in urban areas is associated with an increased risk of SLE. A longer duration of exposure to silica dust is associated with greater risks. This study provides further impetus for additional research into the influence of modifiable exposures on the pathogenesis of SLE.
Design of a Phosphinate‐Based Fluorescent Probe for Superoxide Detection in Mouse Peritoneal Macrophages
Authors: Xu Kehua , Liu Xia , Tang Bo , Yang Guiwen , Yang Yong , An Liguo
Published: October 2006

3′,6′‐Bis(diphenylphosphinyl)fluorescein (PF‐1) was synthesized as a highly selective and sensitive fluorescent probe for imaging O2.− in living cells. The design strategy for the probe was based on the nucleophilic mechanism of O2.− to mediate deprotection of this probe to give fluorescein. Upon reaction with O2.−, the probe exhibits a strong fluorescence response and high selectivity for O2.− over other reactive oxygen species and some biological compounds. The phosphinate‐based probe, as a new fluorescent reagent, is cell‐permeable and can detect micromolar changes of O2.− concentrations by using confocal microscopy in living cells. The unique combination of good selectivity, high sensitivity, good water solubility, and rapid reactivity establishes the potential value of the probe for facilitating investigations of the generation, metabolism, and mechanisms of superoxide‐mediated cellular homeostasis and injury.
Nuclear receptor NR5A2 is required for proper primitive streak morphogenesis
Authors: Labelle‐Dumais Cassandre , Jacob‐Wagner Mariève , Paré Jean‐Francois , Bélanger Luc , Dufort Daniel
Published: October 2006

NR5A2, also known as liver receptor homologue 1 (LRH‐1) and fetoprotein transcription factor (FTF), is an orphan nuclear receptor involved in the regulation of cholesterol metabolism and steroidogenesis in the adult. NR5A2 was also shown to be expressed during early mouse embryogenesis. Consistent with its early expression pattern, a targeted disruption of this gene leads to embryonic lethality around the gastrulation period. To characterize the embryonic phenotype resulting from NR5A2 loss of function, we undertook morphological and marker gene analyses and showed that NR5A2−/− embryos display growth retardation, epiblast disorganization, a mild embryonic–extraembryonic constriction, as well as abnormal thickening of the proximo‐posterior epiblast. We demonstrated that, although initial specification of the anterior–posterior axis occurred in the absence of NR5A2, primitive streak formation was impaired and neither embryonic nor extraembryonic mesoderm was generated. Moreover, although the visceral endoderm does not show major morphological abnormalities in NR5A2−/− embryos, a decrease in the expression level of HNF4 and GATA4 was observed. Aggregation experiments demonstrated that, in the presence of wild‐type tetraploid cells, NR5A2 mutant cells in the epiblast are capable of undergoing normal gastrulation. Therefore, our results suggest a requirement for NR5A2 in extraembryonic tissues and identify a novel role of this gene in proper primitive streak morphogenesis. Developmental Dynamics 235:3359–3369, 2006. © 2006 Wiley‐Liss, Inc.
Expression of claudins in murine tooth development
Authors: Ohazama Atsushi , Sharpe Paul T.
Published: October 2006

Claudins belong to a family of transmembrane proteins that were identified as components of tight junction strands. We carried out comparative in situ hybridization analysis of 11 claudin genes (claudin1 – claudin11) during murine odontogenesis from the formation of the epithelial thickening to the cytodifferentiation stage. We identify dynamic spatiotemporal expression of 9 of the 11 claudins. At the early bell stage, two claudins (claudin1 and 4) are specifically expressed in stratum intemedium, whereas only one claudin is expressed in each of the preameloblasts (claudin2) and preodontoblasts (claudin10). At the bud stage, when the first epithelial differentiation pathways are being established, localized expression of six claudins (claudin1, 3, 4, 6, 7, and 10) identify spatial specific interactions, suggesting a hitherto unobserved complexity of epithelial organization, within the early tooth primordium. Developmental Dynamics 236:290–294, 2007. © 2006 Wiley‐Liss, Inc.
Circulating, soluble forms of major histocompatability complex antigens are not exosome‐associated
Authors: MacKay Philippa A. , LeibundGut‐Landmann Salome , Koch Norbert , Dunn Amy C. , Reith Walter , Jack Ralph W. , McLellan Alexander D.
Published: October 2006

In vitro studies have shown that soluble MHC (sMHC) released by cell lines is bound to nano‐vesicles termed exosomes. It is thought that exosomes may represent the major reservoir of sMHC class I and II molecules in biological fluids. However, most studies have been confined to in vitro assays performed with cell lines. We show here that sMHC in the serum or plasma differs from exosome‐bound sMHC in five ways: In contrast to exosome‐associated sMHC, circulating sMHC is of low density, has a low apparent molecular mass (40–300 kDa) and is not detergent‐labile. Moreover, the majority of MHC class II isoforms and MHC class I in blood are not physically linked and circulating HLA‐DR is accessible to an antibody specific for the HLA‐DR α‐chain intracellular epitope, which is masked by its association with cellular or exosomal membranes. Finally, utilizing transcriptional activator of murine MHC class II (C2ta) promoter‐mutant mice, we showed that the release of sMHC class II into the circulation is dependent on the C2ta pI promoter, but not pIII or pIV. This suggests that myeloid dendritic cells and/or macrophages, which preferentially use promoter pI of the C2ta gene, produce most of the sMHC class II found in the circulation.
Visibility and anonymity effects on attraction and group cohesiveness
Authors: Lea Martin , Spears Russell , Watt Susan E.
Published: October 2006

This study investigated attraction and group cohesiveness under different visibility and anonymity conditions for social categories that differed in their capacity to be visually cued. Using computer‐mediated communication in 36 mixed gender (visually cued category) and nationality (non‐visually cued category) groups, we manipulated social category salience (via discussion topic), and anonymity versus visibility (via live video links). Under high salience, the effects of anonymity versus visibility were moderated by availability of visible category cues. Visibility increased attraction and cohesiveness for visually cued groups, whereas anonymity increased attraction and cohesiveness for non‐visually cued groups. Path analysis showed that, under high salience, effects of visibility and anonymity were mediated by self‐categorization processes, triggered by prototypicality of self in the case of non‐visually cued groups under anonymity. In low salience conditions, visibility directly cued attraction independently from self‐categorization, in line with relational attraction processes. Copyright © 2006 John Wiley & Sons, Ltd.
Cognitive–Emotional–Behavioural Therapy for the eating disorders: working with beliefs about emotions
Authors: Corstorphine Emma
Published: October 2006

A subgroup of eating‐disordered patients have particular difficulty in tolerating negative mood states and existing interventions seem to be less effective when working with such cases. This clinical practice paper outlines a Cognitive–Emotional–Behavioural Therapy (CEBT). This intervention is aimed at enabling patients to challenge the basis of their emotional distress, and thus to reduce the need for the function of the associated eating behaviours. The intervention draws on range of models and techniques, including cognitive behavioural therapy, dialectical behavioural therapy, mindfulness training and experiential exercises. Copyright © 2006 John Wiley & Sons, Ltd and Eating Disorders Association.
Magnetic resonance imaging of phase transitions in nitinol
Authors: Peeters Johannes M. , van Faassen Ernst E.H. , Bakker Chris J.G.
Published: October 2006

Magnetic resonance images are prone to artifacts caused by metallic objects. Apart from being a source of image degradation, such artifacts can also provide information about the magnetic properties of the foreign object. In this work, we aim to explore the potential of magnetic resonance imaging to detect and characterize changes in magnetic properties of nitinol undergoing temperature‐ or strain‐induced phase changes. A spin echo and a gradient echo method were used to measure the magnetization changes related to the phase transformations. Results of both methods were in agreement and in accordance with the independent measurements using a vibrating sample magnetometer. Magnetic resonance imaging turned out to be a suitable method to visualize and quantify magnetization and phase changes in situ. It is not restricted to a single imaging strategy and does not require any modification of the test object. The results indicate the potential of magnetic resonance imaging to provide direct feedback of the thermomechanical state of the alloy. © 2006 Wiley Periodicals, Inc. J Biomed Mater, 2006