bluuebunny/crossref_metadata_2025 huggingface dataset:
DETECTION OF SALMONELLA TYPHIMURIUM IN OYSTERS BY PCR AND MOLECULAR HYBRIDIZATION
Authors: CORRÊA A.A. , TOSO J. , ALBARNAZ J.D. , SIMÕES C.M.O. , BARARDI C.R.M.
Published: October 2006

Because shellfish (oysters, clams and mussels) are filter feeders, i.e., able to concentrate pathogens from the surrounding waters within their tissues, they have been widely associated with outbreaks illness. The incidence of salmonellosis caused by the consumption of raw or undercooked shellfish, is a primary concern of public health agencies. Then, in recent years, more rapid and specific methods based on the DNA sequence of salmonella genes have been developed to detect low levels of pathogens in environmental and food samples. In this study, we developed a sensitive method to detect low levels of Salmonella typhimurium in oyster tissues (0.1 cfu/g). This methodology consisted of dissection of the gastrointestinal oyster tract, pre‐enrichment of the samples in nonselective medium, DNA extraction and polymerase chain reaction followed by molecular hybridization using a digoxygenin‐labeled amplicon‐derived probe. These results can benefit the public health agencies and shellfish producers concerning microbiological and quality aspects of the commercial oyster production.
VALENCIA ORANGE PECTINMETHYLESTERASE MODIFIED PECTIN CHARACTERIZED BY FOURIER TRANSFORM INFRARED SPECTROSCOPY, CHARGE FRACTIONATION AND GELLING
Authors: HUNTER J.L. , THOMAS A.G.A. , DE HASETH J.A. , WICKER L.
Published: October 2006

Pectin was de‐esterified by Valencia orange pectinmethylesterase (PME), fractioned by ion exchange chromatography (IEC) and pooled fractions were characterized for the degree of esterification (%DE) using Fourier transform infrared spectroscopy (FT‐IR), molecular weight (MW) using high‐performance size exclusion chromatography (HPSEC) multi‐angle laser light scattering and calcium gelling properties using texture profile analysis. The experimental %DE of 67.5% was close to the predicted %DE of 67%. The %DE of the pooled pectin fractions decreased slightly with greater elution volume, from 69.3 to 64.0%. The average MW of unfractionated, modified pectin was 268,100. Earlier eluting fractions from IEC had higher MW values near 240,000 than later eluting fractions with MW values near 120,000. PME modified pectin and pectin fractions gelled in the presence of calcium but unmodified pectin did not gel. The hardness and other textural properties of the calcium‐mediated pectin gels were not different among fractions.
A New Frequency Analysis Method for Constructing Fire Histories from Flowering Events in Austral Grasstrees (Xanthorrhoea australis) from Southern Victoria
Authors: MÜLLER GREGG
Published: October 2006

Austral Grasstrees often flower in response to fire, leaving a discernable scar on the trunk. These scars act as a record of flowering, and by measuring the distance between the scars, and relating the growth to a known growth rate, a fire chronology can be constructed from each measured tree. By analysing the frequency distributions of the fire dates calculated from a population of grasstrees, lengthy fire chronologies can be constructed. While the results are provisional, a resolution of two years and spans exceeding 100 years are possible. The technique has considerable advantages over current methods, and should find applications in fire ecology, ecological history and vegetation management.
Sport, Localism and Social Capital in Rural Western Australia
Authors: ATHERLEY KIM M.
Published: October 2006

Whilst there has been some research conducted on the role of sport in Australian rural communities, to date there has been little detailed discussion by social scientists and geographers on the association between sport and social capital. This paper identifies elements of social capital, at a community and regional social scale, which have been expressed through the activities and adaptive strategies of twenty‐five sporting clubs from the wheatbelt region of Western Australia. Most of the adaptive strategies are a direct result of the clubs being exposed to the processes of rural restructuring and include amalgamation and the spatial reorganisation of sporting competition locations. The importance of localism in rural communities is also examined through the issues of trust and distrust within a regional hierarchy context. The paper illustrates how sport is not only an important part of rural life but also an activity which plays an integral role in the formation of bonding and bridging social capital.
Temporal Patterns and Effects of Surface‐Water Diversions on Daily Flows and Aquatic Habitats: Bega‐Bemboka River, New South Wales, Australia
Authors: REINFELDS IVARS , BROOKS ANDREW J. , HAEUSLER TIM , WILLIAMS SIMON
Published: October 2006

An understanding of the nature and magnitude of hydrological, physical habitat and physico‐chemical effects resulting from surface‐water diversions in river systems is essential for effective management of water resources. For most coastal‐draining rivers in New South Wales, however, there are few data available on irrigation diversions, their hydrological impacts and environmental effects. This paper therefore presents an analysis of mean daily surface‐water diversions for pasture irrigation from approximately three years of metered data and the resultant effects on daily flows and aquatic habitats in the Bega‐Bemboka River. The period of analysis of the hydrological effects of irrigation diversions is extended to the full length of record (approximately five years) for gauging stations most affected by irrigation diversions, using Maintenance of Variance Extension Type 1 (MOVE.1) modelling techniques. The annual mean, median and peak daily rates of water diversion by metered surface‐water licences used to irrigate 925 ha of dairy pasture are 10.5 Ml d−1, 7.3 Ml d−1 and 41.5 Ml d−1, respectively. Diversion effects on flow duration statistics are such that the measured 90th and 95th daily flow duration percentiles at the gauging station most affected by upstream irrigation diversions are equivalent to the 97th and 99th flow duration percentiles, respectively, under MOVE.1 modelled natural flow conditions. While diversions for irrigation over the three‐year data period account for only 6.6% of total flow volumes, diversions as a proportion of daily surface‐water inflows increase exponentially under decreasing flow rates. Median and maximum daily diversion rates attain 91% and 118%, respectively, of total surface‐water inflows to the diversion‐affected reach when upstream inflows range from 15 to 20 Ml d−1. This exponentially‐increasing relationship between daily diversion rates and declining surface‐water inflows suggests that ‘rule of thumb’ guidelines on sustainable diversion limits based on mean or median annual percentage diversion volumes need to be applied cautiously to river systems with no or limited capacity to manipulate flows to meet downstream consumptive demands.
“Life Begins When They Steal Your Bicycle”: Cross-Cultural Practices of Personhood at the Beginnings and Ends of Life
Authors: Morgan Lynn M.
Published: October 2006

A friend once told me I was wasting my time writing about cross-cultural perspectives on the beginnings of life. “Your work is interesting for its curiosity value,” he said, “but fundamentally worthless. What happens in other cultures is totally irrelevant to what is happening here.” Those were discouraging words, but as I followed the American debates about the beginnings and ends of life, it seemed he was right. Anthropologists have written a great deal about birth and death rites in other societies and about non-western notions of personhood, but to date our findings have had little impact on American policy, ethics, or law. The recognized experts on contentious topics such as abortion and euthanasia tend to come from the fields of philosophy, bioethics, theology, law, and biology, but rarely from the social sciences. I was a bit surprised, therefore, to be invited to address the Thomas A. Pitts Memorial Lectureship on “Defining the Beginning and the End of Human Life.”
Response to the Summer of 2003 Mediterranean SST Anomalies over Europe and Africa
Authors: Jung Thomas , Ferranti Laura , Tompkins Adrian M.
Published: October 2006

The sensitivity of the atmospheric circulation to the warm Mediterranean sea surface temperature (SST) anomalies observed during the summer of 2003 (July and August) is studied using the European Centre for Medium-Range Weather Forecasts (ECMWF) model. A control integration imposes climatological Mediterranean SSTs as a lower boundary condition. The first sensitivity experiment uniformly increases these Mediterranean SSTs by 2 K, the approximate mean observed in the 2003 summer season. A second experiment then investigates the additional impact of the SST distribution by imposing the observed SST summer anomaly.

The response of the atmospheric circulation in the European area shows some resemblance to the observed anomaly. The weakness of this response suggests, however, that the warm Mediterranean played a minor role, if any, in maintaining the anomalous atmospheric circulation as observed in the summer of 2003. Increasing SST in the Mediterranean locally leads to an increase in precipitation, particularly in the western Mediterranean. Furthermore, significantly increased Sahelian rainfall is simulated, deriving from enhanced evaporation in the Mediterranean Sea. In the ECMWF model the anomalously high moisture is advected by the climatological Harmattan and Etesian winds, where enhanced moisture flux convergence leads to more precipitation. The associated diabatic heating leads to a reduction of the African easterly jet strength. A similar Sahelian response has been previously documented using a different atmospheric model, increasing confidence in the robustness of the result. Finally, the results are discussed in the context of the seasonal predictability of European and African climate.
Glutaredoxins Grx3 and Grx4 regulate nuclear localisation of Aft1 and the oxidative stress response inSaccharomyces cerevisiae
Authors: Pujol-Carrion Nuria , Belli Gemma , Herrero Enrique , Nogues Antoni , de la Torre-Ruiz Maria Angeles
Published: October 2006

Grx3 and Grx4, two monothiol glutaredoxins of Saccharomyces cerevisiae, regulate Aft1 nuclear localisation. We provide evidence of a negative regulation of Aft1 activity by Grx3 and Grx4. The Grx domain of both proteins played an important role in Aft1 translocation to the cytoplasm. This function was not, however, dependent on the availability of iron. Here we demonstrate that Grx3, Grx4 and Aft1 interact each other both in vivo and in vitro, which suggests the existence of a functional protein complex. Interestingly, each interaction occurred independently on the third member of the complex. The absence of both Grx3 and Grx4 induced a clear enrichment of G1 cells in asynchronous cultures, a slow growth phenotype, the accumulation of intracellular iron and a constitutive activation of the genes regulated by Aft1. The grx3grx4 double mutant was highly sensitive to the oxidising agents hydrogen peroxide and t-butylhydroperoxide but not to diamide. The phenotypes of the double mutant grx3grx4 characterised in this study were mainly mediated by the Aft1 function, suggesting that grx3grx4 could be a suitable cellular model for studying endogenous oxidative stress induced by deregulation of the iron homeostasis. However, our results also suggest that Grx3 and Grx4 might play additional roles in the oxidative stress response through proteins other than Aft1.
THE efficacy and safety of transantral ethmoidectomy
Authors: Kimmelman Charles P. , Weisman Robert A. , Osguthorpe J. David , Kay Scott L.
Published: October 2006

With the advent of new endoscopic instruments, rhinologists are reassessing and modifying ethmoidectomy techniques. Despite this renewed interest, the transantral ethmoidectomy has received little attention, even though this procedure has the advantages of avoiding an external incision, safely delineating the medial orbital wall, and simultaneously treating ethmoid and maxillary sinus disease.

The present study compared 74 transantral ethmoidectomy procedures and 47 external ethmoidectomy procedures. The two groups of patients were comparable with respect to age and gender. There was no statistical difference between the two groups with regard to blood loss. Complications were less frequent in the transantral group. Of the 97 patients treated for ethmoid sinusitis, outcome was more successful in the transantral group than in the external ethmoidectomy group when assessed by the need for additional medical or surgical treatment.
Fracture of the proximal humerus with injury to the axillary artery in a boy aged 13 years
Authors: Wera G. D. , Friess D. M. , Getty P. O. , Armstrong D. G. , Lacey S. H. , Baele H. R.
Published: October 2006

Fractures of the proximal humerus with concomitant vascular injury are rare in children. We describe the presentation, diagnosis, and treatment of a fracture of the proximal humerus in association with an axillary artery injury in a child.
Evaluation of ethoxylated alkylsulfate surfactants for use in subsurface remediation
Authors: Rouse Joseph D. , Sabatini David A. , Brown R. Eric , Harwell Jeffrey H.
Published: October 2006

Experiments were conducted to evaluate the potential of ether sulfate surfactants with degrees of ethoxylation ranging from one to four per molecule for use in subsurface remediation. It was hypothesized that ethoxylated anionic surfactants will exhibit lower losses in the subsurface due to precipitation and sorption as a function of increasing ethoxylation while maintaining high hydrocarbon solubilization potentials. Results demonstrated that no significant precipitation of surfactant and calcium occurred where the degree of ethoxylation was two or greater. Sorption assays demonstrated that these ethoxylated anionic surfactants were less prone to sorption on soil than nonethoxylated anionic and nonionic surfactants. Furthermore, enhancements in solubilization of naphthalene were evidenced with increasing degrees of ethoxylation, and micelle‐water partition coefficients were comparable with those of other high‐performance surfactants. Microbial degradation assays indicated that these ethoxylated anionic surfactants served readily as substrates, raising concerns relative to their use in subsurface aerobic systems. However, they could be compatible with a treatment train concluded with a biological unit process.
When vying reveals lying: the timed antagonistic response alethiometer
Authors: Gregg Aiden P.
Published: October 2006

Two experiments tested a new computer‐based lie‐detection technique. The Timed Antagonistic Response Alethiometer (TARA) manufacturers a situation in which, if respondents lie, they must perform two incompatible tasks, whereas if they tell the truth, they can perform two compatible ones. Both tasks involve repeatedly classifying target and control statements as true or false. The incompatible task combination, being more difficult, takes longer to complete correctly; hence, slower responses diagnose dishonesty. Experiment 1 found that, while concurrently classifying control statements honestly, participants invariably took longer to classify target statements dishonestly than honestly. Exploiting this effect, Experiment 2 found that separate groups of liars and truth‐tellers could be distinguished with about 85% accuracy. The properties and potential of the technique are discussed. Copyright © 2006 John Wiley & Sons, Ltd.
Cover Picture: Metal–Silica Hybrid Nanostructures for Surface‐Enhanced Raman Spectroscopy (Adv. Mater. 21/2006)
Authors: Schierhorn M. , Lee S. J. , Boettcher S. W. , Stucky G. D. , Moskovits M.
Published: October 2006

The image shows an ordered array of silver‐tipped silica nanorods, which serve as a substrate for surface enhanced Raman spectroscopy (SERS). Signal intensities from test molecules in regions of aggregated pillars (indicated by the green laser beam) were enhanced by factors of 10 to 20 compared to arrays of separated pillars, as reported by Moskovits and co‐workers on p. 2829. This hybrid structure maximizes SERS signal intensities from analytes while minimizing the quantities needed for detection due to the precise formation of “hot regions” at the intersection of the silver tips.
Nonstationary model of the semicontinuous depolymerization of polycarbonate
Authors: Piñero‐Hernanz Raúl , García‐Serna Juan , Cocero María José
Published: October 2006

The experimental work for the depolymerization process of Bisphenol A polycarbonate pellets and CD/DVD wastes in a semicontinuous reactor and a novel nonstationary model to describe the process is presented. The different steps of the process to develop the model are analyzed thoroughly. The kinetics of the alkali‐catalyzed methanolysis of polycarbonate was determined. The reactor and kinetic models were validated by a series of 21 experiments performed in a laboratory semicontinuous tubular reactor at isothermal conditions from 90 to 180°C and pressures from 1.0 to 20.0 MPa in liquid phase, with and without NaOH concentrations of 1 × 10−3 to 5 × 10−3 kg/L, flow rates from 2.3 × 10−3 to 10.2 × 10−3 L/min, and CO2 molar fractions from zero to 0.374. The effects of temperature, pressure, catalyst amount, mass transfer (solvent flow rate), and CO2 addition in kinetics were investigated. © 2006 American Institute of Chemical Engineers AIChE J, 2006
New procedure for derivation of approximations for temperature integral
Authors: Chen Haixiang , Liu Naian
Published: October 2006

A new procedure for the derivation of the approximations for temperature integral from its derivatives is presented. This procedure can produce a series of the approximations, including some published and some new ones. By combining the different order derivatives of temperature integral, a new approximation is proposed. The corresponding equation for the evaluation of kinetic parameters can be put in the form

The validity of the new approximation has been tested with the true value of temperature integral from numerical calculation. Compared with several published approximations, the new one has the highest accuracy and at the same time retains simplicity, which indicates it is a good approximation for the evaluation of kinetic parameters from nonisothermal kinetic analysis. © 2006 American Institute of Chemical Engineers AIChE J, 2006
Liquid‐liquid two‐phase flow patterns in a rectangular microchannel
Authors: Zhao Yuchao , Chen Guangwen , Yuan Quan
Published: October 2006

In this work, the flow of immiscible fluids in a PMMA microchannel 300 μm wide and 600 μm deep was investigated experimentally. Dyed de‐ionized water and kerosene were selected as the test fluids. Flow patterns were observed by using a CCD camera and were identified by examining the video images. Flow patterns obtained at the T‐junction and in the microchannel are presented. Superficial velocities varied between 9.26 × 10−4 ∼ 1.85 m/s for water and 9.26 × 10−4 ∼ 2.78 m/s for kerosene. The formation mechanism of slug, monodispersed droplet and droplet populations at the T‐junction was studied. Weber numbers of water and kerosene, WeKS and WeWS, were used to predict the flow regime transition and the flow patterns map. The experimental data of volume of dispersed phase were successfully correlated as a function of WeKS, WeWS, and hold‐up fraction. Considering the uncertainty associated with experimental quantification of the process, the results are in satisfactory agreement over the wide range of 1.90 × 10−3 < WeWS < 30.43 and 5.90 × 10−6 < WeKS < 0.13 with average absolute deviation of only 16.18%. © 2006 American Institute of Chemical Engineers AIChE J, 2006
Poly(caprolactone) thin film preparation, morphology, and surface texture
Authors: Simon Darren , Holland Anthony , Shanks Robert
Published: October 2006

The properties and surface uniformity of poly‐ (caprolactone) (PCL) thin films were measured. Thin films were prepared using a spin‐coating technique. Film thickness and roughness were correlated with variation in solution concentration, spinning speed and spinning time. Differential scanning calorimetry (DSC) was used to investigate the crystallization and melting processes. The enthalpy of melting variation correlated with the film thickness, while melting temperature was independent of film thickness. In addition, surface roughness was found to be a function of PCL thickness. Film thickness and roughness showed a progressive decrease when spinning speed was increased, while spinning time provided no significant influence on film thickness. PCL thickness and roughness significantly increased when PCL solution concentration increased. Hot stage optical microscopy showed that larger spherulitic crystals were present in thin films, and the smaller crystals present in thicker films had a coarser texture consistent with increased surface roughness. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 1287–1294, 2007
High temperature stability of different polymer‐modified bitumens: A rheological evaluation
Authors: Pérez‐Lepe A. , Martínez‐Boza F. J. , Gallegos C.
Published: October 2006

Polymer‐modified binders are increasingly used by the pavement industry. In practice, the bituminous binders are stored at high temperatures previous to its application on the road. The instability problems of the bitumen due to the polymer‐rich phase separation may affect the final properties of the pavement. Most polymers tend to be insoluble, to some degree, in the bitumen matrix, and phase separation may result. Chemical compatibility between the polymer additive and the bitumen, and processing conditions, are crucial to obtain suitable properties of the polymer‐modified bitumens. In this work, different polymer‐modified binders were manufactured by using a high‐shear mixing device. Once a good mechanical dispersion of the polymer in the bitumen matrix was achieved, the binders were stored in tubes at high temperatures. During the storage, the unstable polymer‐rich phase segregates and starts to ascend up to the surface. The progression of the polymer phase separation was followed through the evolution of the linear viscoelastic and the viscous properties of the samples collected, after different storage periods, from the top part of the storage tube. From the experimental results obtained, we may conclude that the use of a reactive polymer as additive is a promising alternative to obtain more stable binders. © 2006 Wiley Periodicals, Inc. J Appl PolymSci 103: 1166–1174, 2007
Effect of interchain interactions on the translocation of polymer chains through small holes
Authors: Wang Chao , Luo Meng‐Bo
Published: October 2006

The translocation of polymer chains through a small hole was simulated with the dynamic Monte Carlo method. The dependence of the relaxation time (τ1) and escaping time (τ2) on the chain concentration (C) was studied. The interchain interaction played an important role in the translocation process. Different behaviors were discovered at low and highCregions. τ1presented a power law behavior withCat low and highCvalues with exponents of −1 and −3, respectively. τ2was roughly independent ofCat lowCvalues but decreased with power law exponent −1.3 at highCvalues. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 1200–1205, 2007
Effectiveness of protected area networks in representing freshwater biodiversity: the case of a Mediterranean river basin (south‐eastern Spain)
Authors: Abellán Pedro , Sánchez‐Fernández David , Velasco Josefa , Millán Andrés
Published: October 2006

Biodiversity is probably at greater risk in freshwater systems than in other ecosystems. Although protected areas (PAs) play a vital role in the protection of biodiversity and are the mainstay of most conservation polices, the coverage of biodiversity by existing PA networks is often inadequate and few reserves are created that take into consideration freshwater biota.

In this paper an attempt is made to address the performance of protected areas in the context of freshwater biodiversity conservation using data records for water beetles in a Mediterranean river basin.

Although the present PAs in the study area cover a relatively high number of water beetle species, the distribution and extent of reserves is still inadequate or insufficient to protect freshwater biodiversity, especially species of conservation concern.

Alternative area‐selection methods (hotspots and complementary) were more efficient than PAs for representing water beetles. Within these, complementarity was the most efficient approach, and was able to represent all species in a significantly lower area than the current PA network. On the other hand, the future Natura 2000 Network will result in a great increase in the total area of protected land as well as in the biodiversity represented.

Unfortunately, the occurrence of a species within a protected area is not a guarantee of long‐term survival because the extent of PAs is often insufficient and disturbances occur outside park boundaries. Thus, whole‐catchment management and natural‐flow maintenance are indispensable strategies for freshwater biodiversity conservation.

Copyright © 2006 John Wiley & Sons, Ltd.
Patients with juvenile psoriatic arthritis comprise two distinct populations
Authors: Stoll Matthew L. , Zurakowski David , Nigrovic Lise E. , Nichols David P. , Sundel Robert P. , Nigrovic Peter A.
Published: October 2006

Objective

Psoriatic arthritis (PsA) in children is clinically heterogeneous. We examined a large population of children with juvenile PsA for evidence of phenotypic clustering that could suggest the presence of distinct clinical entities.

Methods

We reviewed the medical records of 139 patients meeting the Vancouver criteria for juvenile PsA. To identify segregation into phenotypic groups, we compared younger patients with their older counterparts and subjected the whole population to 2‐step cluster analysis.

Results

Among patients with juvenile PsA, the age at onset is biphasic, with peaks occurring at approximately 2 years of age and again in late childhood. Compared with children ages 5 years and older, younger patients are more likely to be female, exhibit dactylitis and small joint involvement, and express antinuclear antibodies. Progression to polyarticular disease (≥5 joints) is more common in younger children, although joint involvement remains oligoarticular in the majority of children. In contrast, older patents tend to manifest enthesitis, axial joint disease, and persistent oligoarthritis. Uveitis is equally represented in both age groups. Despite a higher utilization of methotrexate therapy, younger patients required, on average, more than twice as long to achieve clinical remission (23 months versus 9.2 months; P = 0.044). Cluster analysis identified largely overlapping subgroups but suggested that the presence of dactylitis, rather than age, has the greatest capacity to predict essential features of the clinical phenotype.

Conclusion

Juvenile PsA comprises 2 distinct populations of patients. Although the pathophysiologic correlate of this finding remains undefined, future studies should avoid the assumption that PsA in childhood constitutes a single etiologic entity.
Macrophage migration inhibitory factor promoter polymorphisms and the clinical expression of scleroderma
Authors: Wu Sou‐Pan , Leng Lin , Feng Zeny , Liu Nianjun , Zhao Hongyu , McDonald Courtney , Lee Annette , Arnett Frank C. , Gregersen Peter K. , Mayes Maureen D. , Bucala Richard
Published: October 2006

Objective

To investigate the potential association between functional polymorphisms in the gene for the innate mediator, macrophage migration inhibitory factor (MIF), and the clinical expression of systemic sclerosis (SSc).

Methods

Genomic DNA samples and clinical data were collected from the Scleroderma Family Registry and DNA Repository at the University of Texas Health Science Center at Houston. A total of 740 subjects were studied; 203 of them had diffuse cutaneous SSc (dcSSc), 283 had limited cutaneous SSc (lcSSc), and the remaining 254 healthy subjects served as controls. Association analyses were performed on the whole data set and on patient and sex subsets. Significant relationships were determined between clinical variables and MIF polymorphisms for each disease subtype in the studied groups.

Results

The frequency of the −173*C MIF allele, which was previously reported to be associated with high production of MIF, was lower in the lcSSc group (12.6%) than in the dcSSc (19.2%) or control (18.5%) groups (P = 0.010 and P = 0.011, respectively). Haplotype analysis for 2 closely linked polymorphisms in the MIF promoter showed that in white subjects with lcSSc or dcSSc, the lcSSc population had a significantly lower representation of the high‐expression MIF haplotype defined by −173*C and −794 with 7 CATT repeats (C7) (P = 0.015, odds ratio 1.94 [95% confidence interval 1.14–3.32]). Fibroblasts encoding the C7 MIF haplotype were observed to produce more MIF upon in vitro stimulation than those with a non‐C7 haplotype.

Conclusion

Functional promoter polymorphisms in the MIF gene affect the clinical presentation of SSc. The proinflammatory haplotype defined by C7 is underrepresented in patients with lcSSc.
Long‐term outcome and prognostic factors in enthesitis‐related arthritis: A case–control study
Authors: Flatø Berit , Hoffmann‐Vold Anna‐Maria , Reiff Andreas , Førre ØYstein , Lien Gunnhild , Vinje Odd
Published: October 2006

Objective

To compare the clinical, functional, and radiographic outcomes in patients with enthesitis‐related arthritis (ERA) with those in patients with other subtypes of juvenile idiopathic arthritis (JIA) and healthy controls, and to determine genetic markers, patient characteristics, and early disease variables that predict the development of remission, sacroiliitis, and physical limitations in ERA.

Methods

Fifty‐five children with ERA who were first admitted to Rikshospitalet Medical Center between 1980 and 1985 were studied. Patients with oligoarthritis or polyarthritis who were admitted during the same period (n = 55) and individuals from a national population registry (n = 55) were matched for sex and age and used as controls. Health status was assessed after a median of 15.3 years of disease (range 11.7–21.9 years) and, in some patients, was reassessed after a median of 23.0 years (range 19.7–29.4 years) of disease, by use of the 36‐item Short Form health survey and the Health Assessment Questionnaire. Clinical and radiographic examinations were performed at the 15‐year followup visit. Variables relating to the onset of disease were retrospectively obtained by chart review. HLA alleles were determined by genotyping and serologic testing.

Results

Patients with ERA had lower levels of physical functioning, poorer physical health, and more bodily pain compared with patients with oligoarthritis or polyarthritis (after a median of 15.3 and a median of 23.0 years) and normal controls (after a median of 15.3 years). Among patients with ERA, remission occurred in 44%, sacroiliitis was observed in 35%, and reduced spinal flexion was observed in 75%. Predictors of failure to attain disease remission included the following: ankylosing spondylitis (AS) in a first‐degree relative, the presence of HLA–DRB1*08, and ankle arthritis within the first 6 months. HLA–DPB1*02 was a protective factor, whereas a persistently elevated erythrocyte sedimentation rate (ESR), and hip arthritis within the first 6 months were risk factors for sacroiliitis. Female sex, a family history of AS, and high numbers of affected joints within the first 6 months predicted poor physical health status after 23 years. Male sex was associated with reduced anterior flexion of the spine.

Conclusion

In this study, patients with ERA had poorer physical outcomes compared with patients with oligoarticular or polyarticular JIA and controls from the general population. A family history of related diseases, sex, the presence of HLA–DRB1*08, the absence of HLA–DPB1*02, a persistently elevated ESR, early hip or ankle arthritis, and high numbers of affected joints were predictors of an unfavorable outcome.
Myofibroblasts and hyalinized collagen as markers of skin disease in systemic sclerosis
Authors: Kissin Eugene Y. , Merkel Peter A. , Lafyatis Robert
Published: October 2006

Objective

To investigate the correlation between the degree of dermal fibrosis and myofibroblast infiltration using clinical assessments of skin thickness and hardness in systemic sclerosis (SSc).

Methods

Eleven patients with diffuse SSc and 10 healthy controls were evaluated using the modified Rodnan skin thickness score and durometry (hardness measurement). Biopsy samples were obtained from the dorsal mid‐forearm in all subjects at the baseline visit and again 6–12 months later in patients with SSc. Five of the patients with SSc received treatment with cyclophosphamide (CYC) in the interval between skin biopsies. Biopsy sections were assessed for myofibroblast and hyalinized collagen content by 2 blinded observers.

Results

Myofibroblast and hyalinized collagen scores each correlated with the forearm skin score (r = 0.83, P < 0.0001 and r = 0.78, P < 0.0001, respectively) and with the forearm durometry score (r = 0.72, P < 0.0004 and r = 0.69, P < 0.0008, respectively). The change in the dermal hyalinized collagen score correlated with the change in the forearm durometry score (r = 0.74, P < 0.0213). The myofibroblast score decreased in all 5 patients who received CYC and increased in those receiving non‐CYC treatments (P < 0.01 for the difference).

Conclusion

Myofibroblasts play an important role in the pathogenesis of fibrosis, and our data imply that quantification of myofibroblasts and hyalinized collagen in skin may be a useful outcome measure in clinical studies of SSc.
Effectiveness of tumor necrosis factor inhibitors in rheumatoid arthritis in an observational cohort study: Comparison of patients according to their eligibility for major randomized clinical trials
Authors: Zink Angela , Strangfeld Anja , Schneider Matthias , Herzer Peter , Hierse Franka , Stoyanova‐Scholz Maria , Wassenberg Siegfried , Kapelle Andreas , Listing Joachim
Published: October 2006

Objective

Randomized clinical trials (RCTs) evaluate the efficacy of treatments in selected groups of patients defined by strict inclusion criteria. The value of these trials in predicting therapeutic effectiveness in “real world” patients is limited. This observational cohort study was designed to complement the knowledge obtained in RCTs by evaluating the effectiveness of tumor necrosis factor (TNF) inhibitors in patients with rheumatoid arthritis (RA) according to their eligibility for the major trials.

Methods

Using the data from the German biologics register Rheumatoid Arthritis Observation of Biologic Therapy (RABBIT [in German]), we investigated how many of the RA patients who were treated with a TNF inhibitor (infliximab, etanercept, or adalimumab) would have been eligible for the major clinical trials that led to approval of the drugs. In addition, therapeutic effectiveness was compared in the eligible and ineligible patients using the American College of Rheumatology 20% (ACR20) and 50% (ACR50) improvement response criteria.

Results

Only 21–33% of the patients in the RABBIT register would have been eligible for the major trials. In these patients, the ACR20 and ACR50 improvement responses, indicating therapeutic effectiveness, were comparable with the response rates in the published trials. ACR response rates were lower in those patients considered ineligible for the trials; however, absolute improvement was similar to that in eligible patients. Ineligible patients had lower baseline disease activity, more comorbidity, and lower functional status.

Conclusion

RCT cohorts reflect only a minor proportion of the patients treated with biologic agents in routine care. In the clinic setting, the indications for treatment with biologic agents are not identical to the inclusion criteria for trials. Despite the smaller relative improvement achieved in these patients with longstanding, severe RA who would not fulfill the inclusion criteria of a major trial, the majority of such patients would nevertheless benefit from biologic therapy.
The effect of moderate‐dose corticosteroids in preventing severe flares in patients with serologically active, but clinically stable, systemic lupus erythematosus: Findings of a prospective, randomized, double‐blind, placebo‐controlled trial
Authors: Tseng Chung‐E , Buyon Jill P. , Kim Mimi , Belmont H. Michael , Mackay Meggan , Diamond Betty , Marder Galina , Rosenthal Pamela , Haines Kathleen , Ilie Virginia , Abramson Steven B.
Published: October 2006

Objective

Serial measurements of anti–double‐stranded DNA (anti‐dsDNA) and complement are routine in the management of systemic lupus erythematosus (SLE), but their utility as biomarkers in preemptive treatment to prevent flares remains a subject of controversy. We hypothesized that concomitant elevation of anti‐dsDNA and C3a can predict SLE activity in patients with stable or inactive disease and that short‐term treatment with corticosteroids can avert flares.

Methods

In this prospective, randomized, double‐blind, placebo‐controlled trial, 154 patients were evaluated monthly for up to 18 months, with measurements of C3a, C3, C4, CH50, and anti‐dsDNA levels. Patients who remained clinically stable but showed serologic evidence of an SLE flare (elevation of both the anti‐dsDNA level by 25% and the C3a level by 50% over the previous 1–2 monthly visits) were randomized to receive either prednisone or placebo therapy at a dosage of 30 mg/day for 2 weeks, 20 mg/day for 1 week, and 10 mg/day for 1 week.

Results

Forty‐one patients (21 randomized to prednisone and 20 randomized to placebo) experienced a serologic flare. Analysis of severe flares occurring ≤90 days from randomization revealed that 6 occurred in patients taking placebo and none occurred in patients taking prednisone (P = 0.007). Severe flares resulted in an increase in the prednisone dosage to >40 mg/day and/or the addition of an immunosuppressive agent. Furthermore, improvement in scores on the Systemic Lupus Erythematosus Disease Activity Index, decreased levels of anti‐dsDNA antibodies, and increased levels of C4 occurred 1 month after initiation of prednisone treatment.

Conclusion

These preliminary data support our hypothesis that in a subset of clinically stable SLE patients with a combination of elevated C3a and anti‐dsDNA levels, short‐term corticosteroid therapy may avert a severe flare.
HLA polymorphisms in African Americans with idiopathic inflammatory myopathy: Allelic profiles distinguish patients with different clinical phenotypes and myositis autoantibodies
Authors: O'Hanlon Terrance P. , Rider Lisa G. , Mamyrova Gulnara , Targoff Ira N. , Arnett Frank C. , Reveille John D. , Carrington Mary , Gao Xiaojiang , Oddis Chester V. , Morel Penelope A. , Malley James D. , Malley Karen , Shamim Ejaz A. , Chanock Stephen J. , Foster Charles B. , Bunch Thomas , Reed Ann M. , Love Lori A. , Miller Frederick W.
Published: October 2006

Objective

To investigate possible associations of HLA polymorphisms with idiopathic inflammatory myopathy (IIM) in African Americans, and to compare this with HLA associations in European American IIM patients with IIM.

Methods

Molecular genetic analyses of HLA–A, B, Cw, DRB1, and DQA1 polymorphisms were performed in a large population of African American patients with IIM (n = 262) in whom the major clinical and autoantibody subgroups were represented. These data were compared with similar information previously obtained from European American patients with IIM (n = 571).

Results

In contrast to European American patients with IIM, African American patients with IIM, in particular those with polymyositis, had no strong disease associations with HLA alleles of the 8.1 ancestral haplotype; however, African Americans with dermatomyositis or with anti–Jo‐1 autoantibodies shared the risk factor HLA–DRB1*0301 with European Americans. We detected novel HLA risk factors in African American patients with myositis overlap (DRB1*08) and in African American patients producing anti–signal recognition particle (DQA1*0102) and anti–Mi‐2 autoantibodies (DRB1*0302). DRB1*0302 and the European American–, anti–Mi‐2–associated risk factor DRB1*0701 were found to share a 4–amino‐acid sequence motif, which was predicted by comparative homology analyses to have identical 3‐dimensional orientations within the peptide‐binding groove.

Conclusion

These data demonstrate that North American IIM patients from different ethnic groups have both shared and distinct immunogenetic susceptibility factors, depending on the clinical phenotype. These findings, obtained from the largest cohort of North American minority patients with IIM studied to date, add additional support to the hypothesis that the myositis syndromes comprise multiple, distinct disease entities, perhaps arising from divergent pathogenic mechanisms and/or different gene–environment interactions.
Low predictive accuracy of the Kattan postoperative nomogram for renal cell carcinoma recurrence in a population of French patients
Authors: Hupertan Vincent , Roupret Morgan , Poisson Jean‐Francois , Chretien Yves , Dufour Bertrand , Thiounn Nicolas , Mejean Arnaud
Published: October 2006

BACKGROUND.

The aim of the current study was to establish the predictive accuracy of the Kattan postoperative nomogram for nonmetastatic renal cell carcinoma (RCC) by comparing predictions with actual disease recurrence in patients who underwent surgery in a single center in France.

METHODS.

Between 1985 and 2000, 844 patients were treated for RCC. The following data were collated: age, symptoms, histology, tumor size, grade, TNM 1997 stage, recurrence, and progression. For each patient a prognostic score (predicted probability) for recurrence‐free survival (RFS) at 5 years was calculated using the Kattan nomogram. The discriminating ability of the model was assessed by Harrell's concordance index (c‐index). Bootstrapping was used to assess confidence intervals. Furthermore, survival was then estimated by the Kaplan‐Meier method and Cox proportional hazards regression analysis.

RESULTS.

In all, 565 patients (median age, 62 years) were included. At the time of the last follow‐up, 81 patients had died and 101 had experienced RCC recurrence. The c‐index for RFS (Kattan nomogram) was only 0.607 (95% confidence interval [CI]: 0.576–0.635). The 5‐year RFS rate and cancer‐specific survival rate were 81.5% and 84.7%, respectively. Of the 4 variables included in the nomogram, only TNM stage was associated with recurrence in a multivariate analysis (Cox analysis) (P = .022).

CONCLUSIONS.

There was a discrepancy between predicted RFS as estimated by the Kattan nomogram and the likelihood of being recurrence‐free at 5 years according to the Cox analysis in the current population of patients. However, until new dynamic models become available clinicians may still improve their predictive ability by using the current nomogram. Cancer 2006. © 2006 American Cancer Society.
Expression of Hand2 is sufficient for neurogenesis and cell type–specific gene expression in the enteric nervous system
Authors: Hendershot Tyler J. , Liu Hongbin , Sarkar Anjali A. , Giovannucci David R. , Clouthier David E. , Abe Makoto , Howard Marthe J.
Published: October 2006

The basic helix‐loop‐helix DNA binding protein Hand2 is expressed in neural crest–derived precursors of enteric neurons and has been shown to affect both neurogenesis and neurotransmitter specification of noradrenergic sympathetic ganglion neurons. In the current study, our goal was to determine whether Hand2 affects neurogenesis and/or expression of vasoactive intestinal polypeptide and choline acetyltransferase in developing enteric neurons. Gain‐of‐function of Hand2 in HNK‐1+ immmunoselected precursor cells resulted in increased neurogenesis. The number of neurons expressing vasoactive intestinal polypeptide increased in response to Hand2 overexpression although choline acetyltransferase was not affected. Targeted deletion of Hand2 in neural crest cells resulted in loss of all neurons expressing vasoactive intestinal polypeptide along the length of the gastrointestinal tract, patterning defects in the myenteric plexus of the stomach, and altered number and morphology of neurons expressing TH. Our data demonstrate that expression of Hand2 is sufficient and necessary for neurogenesis and expression of a subset of cell type‐specific markers in the developing enteric nervous system. Developmental Dynamics 236:93–105, 2007. © 2006 Wiley‐Liss, Inc.
Combinatorial expression patterns of heparan sulfate sulfotransferases in zebrafish: I. The 3‐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 3‐O‐sulfotransferases (3‐OST) catalyze the transfer of sulfate groups to the 3‐O position of glucosamine residues of HS, a rare, but essential HS chain modification required for HS fine structure. We report here the first characterization and developmental expression analysis of the 3‐OST gene family in a vertebrate. There are eight 3‐OST genes in zebrafish: seven genes with homology to known 3‐OST genes in mouse and human, as well as a novel, 3‐OST‐7. A phylogenetic comparison of human, mouse, and zebrafish indicates the 3‐OST family can be subdivided into two distinct subgroups. We examined the mRNA expression patterns in several tissues/organs throughout early zebrafish development, including early cleavage stages, somites, brain, internal body organ primordial, and pectoral fin development. The 3‐OST gene family has both specifically expressed and ubiquitously expressed genes, suggesting in vivo functional differences exist between members of this family. Developmental Dynamics 235:3423–3431, 2006. © 2006 Wiley‐Liss, Inc.
Differential expression of anti‐Müllerian hormone (amh) and anti‐Müllerian hormone receptor type II (amhrII) in the teleost medaka
Authors: Klüver Nils , Pfennig Frank , Pala Irene , Storch Katja , Schlieder Marlen , Froschauer Alexander , Gutzeit Herwig O. , Schartl Manfred
Published: October 2006

In mammals, the anti‐Müllerian hormone (Amh) is responsible for the regression of the Müllerian ducts; therefore, Amh is an important factor of male sex differentiation. The amh gene has been cloned in various vertebrates, as well as in several teleost species. To date, all described species show a sexually dimorphic expression of amh during sex differentiation or at least in differentiated juvenile gonads. We have identified the medaka amh ortholog and examined its expression pattern. Medaka amh shows no sexually dimorphic expression pattern. It is expressed in both developing XY male and XX female gonads. In adult testes, amh is expressed in the Sertoli cells and in adult ovaries in granulosa cells surrounding the oocytes, like in mammals. To better understand the function of amh, we cloned the anti‐Müllerian hormone receptor type II (amhrII) ortholog and compared its expression pattern with amh, aromatase (cyp19a1), and scp3. During gonad development, amhrII is coexpressed with medaka amh in somatic cells of the gonads and shows no sexually dimorphic expression. Only the expression level of the Amh type II receptor gene was decreased noticeably in adult female gonads. These results suggest that medaka Amh and AmhrII are involved in gonad formation and maintenance in both sexes. Developmental Dynamics 236:271–281, 2007. © 2006 Wiley‐Liss, Inc.