bluuebunny/crossref_metadata_2025 huggingface dataset:
Distribution of immunodeficiency fact files with XML – from Web to WAP
Authors: Väliaho Jouni , Riikonen Pentti , Vihinen Mauno
Published: June 2005

Background

Although biomedical information is growing rapidly, it is difficult to find and retrieve validated data especially for rare hereditary diseases. There is an increased need for services capable of integrating and validating information as well as proving it in a logically organized structure. A XML-based language enables creation of open source databases for storage, maintenance and delivery for different platforms.

Methods

Here we present a new data model called fact file and an XML-based specification Inherited Disease Markup Language (IDML), that were developed to facilitate disease information integration, storage and exchange. The data model was applied to primary immunodeficiencies, but it can be used for any hereditary disease. Fact files integrate biomedical, genetic and clinical information related to hereditary diseases.

Results

IDML and fact files were used to build a comprehensive Web and WAP accessible knowledge base ImmunoDeficiency Resource (IDR) available at http://bioinf.uta.fi/idr/. A fact file is a user oriented user interface, which serves as a starting point to explore information on hereditary diseases.

Conclusion

The IDML enables the seamless integration and presentation of genetic and disease information resources in the Internet. IDML can be used to build information services for all kinds of inherited diseases. The open source specification and related programs are available at http://bioinf.uta.fi/idml/.
The birth of a hybrid: the shaping of the Australian radio industry
Authors: Griffen-Foley Bridget
Published: June 2005

This article surveys the emergence and evolution of the Australian radio system, a hybrid system that by the 1930s embraced both public and private broadcasters. It examines the ways in which proponents of Australian broadcasting viewed developments in Britain and the United States;
the debate about cultural standards reflected in arguments about the merits of public sector and commercial broadcasting; the influence of American advertising agencies on Australian programming; and the emergence of an Australian advertising and production infrastructure. In sketching more
recent developments, the article argues that Australian broadcasting history should be seen as a continuing struggle between large commercial proprietors that wish to extend their reach over the entire nation and those interests that seek to preserve the local and regional character of radio.
Programme-makers on Parker: occupational reflections on the radio production legacy of Charles Parker
Authors: Street Seán
Published: June 2005

Charles Parker was born in Bournemouth on 5 April 1919. Throughout the seventeen years that this report's author has taught radio in the Bournemouth Media School at the town's university - and for most of his career as a programme-maker - he has held an ambition to celebrate Parker
in his birthplace. Last year the Broadcasting History Group was established within the Media School and, with the help of research funding, set about establishing a number of initiatives to explore aspects of broadcasting's short but significant past. The first of these initiatives to bear
visible fruit has been Charles Parker Day, a one-day conference held on the producer's birthday: this report has been drawn from the first Charles Parker Day Conference, held in Bournemouth (UK), on 5 April 2004.
Fusion von Sensordaten am Beispiel von Sicherheitsanwendungen in der Automobiltechnik (Sensor Data Fusion for Safety Applications in Automotive Environment)
Authors: Skutek Michael , Linzmeier Dirk
Published: June 2005

Der Artikel beschreibt unterschiedliche Ansätze zur Fusion von Sensordaten beispielhaft an zwei Sicherheitsanwendungen im Automobilbereich – PreCrash und Fußgängererkennung. Der Fokus liegt nicht ausschließlich auf der Fusionstheorie selbst; auch die Anforderungen der Anwendungen und die sensortechnischen Voraussetzungen sind dargestellt.

Für die PreCrash-Funktion werden zwei Ansätze zur Fusion von Radarsensoren und einem Laserscanner vorgestellt. Das Fußgängerdetektionssystem besteht aus einer Anordnung von Thermopile-Sensoren, die zur Bestimmung der Fußgängerposition fusioniert werden.
The U.S.-Japan Security Alliance, ASEAN, and the South China Sea Dispute
Authors: Rowan Joshua P.
Published: June 2005

The situation in the South China Sea—where sovereignty and oil and natural gas interests are converging—creates a flashpoint with significant policy implications for the U.S., Japan, and other Asian nations. Only the U.S.-Japan security alliance, operating in conjunction with the Association of Southeast Asian Nations, can safely foster a long-term solution.
SARS in Asia: Crisis, Vulnerabilities, and Regional Responses
Authors: Caballero-Anthony Mely
Published: June 2005

This article examines lessons learned from the recent Severe Acute Respiratory Syndrome crisis in East and Southeast Asia, arguing that the wide-ranging impact of infectious diseases makes it imperative for states to treat these diseases as security concerns. “Securitizing” infectious diseases provides urgency for mobilizing resources and strengthening regional cooperation. Adding infectious diseases to the security agenda allows for better handling of sudden outbreaks that endanger lives and threaten the survival of nation-states; this is also in line with the region's concept of comprehensive security.
The Amateur's Lightning Rod: DV Documentary in Postsocialist China
Authors: Wang Yiman
Published: June 2005

Abstract This article examines the cultural politics of DV documentaries emerging from postsocialist China, discussing the documentary-makers as amateur-authors. It goes on to argue that the documentarians' self-consciously deployed aesthetics of cruelty constitutes a socio-political claim for an alternative “real,” derived from a subaltern “structure of feeling.”
In the Cut
Authors: Park Douglas , Dietrich Dawn
Published: June 2005

Abstract Jane Campion's newest film, In the Cut, confounded critics, as it leaves her familiar territory of Anglo Australia and a high literary mode for New York City and the pop culture associations of a slasher/thriller. Transcending genre, the screenplay and cinematography unconventionally render a psychic landscape of female desire and romantic longing surviving in a male urban wasteland.
Hero
Authors: Zhang Jia-xuan
Published: June 2005

Abstract: Is Hero just another martial-arts film? Who is the hero in Hero? Does the film suggest a justification for the despotism in Chinese history, as many Chinese critics have charged? Is there any connection between Hero and Zhang Yimou's previous works? This review focuses on these challenging questions as it explores the intricacies of Hero.
Effect of LH on prostaglandin F2α and prostaglandin E2 secretion by cultured porcine endometrial cells
Authors: Blitek Agnieszka , Ziecik Adam J
Published: June 2005

LH appears to be a potent stimulator of the release of endometrial prostaglandins (PGs) in the pig. The aim of the present studies was to examine the effect of LH on PGF2αand PGE2secretion by cultured porcine endometrial cells on days 10–12 and 14–16 of the oestrous cycle and to compare its action with oxytocin. A time-dependent effect of LH (10 ng/ml) on PGF2αrelease from luminal epithelial and stromal cells on days 10–12 was observed (experiment 1). The highest increase in PGF2αsecretion in response to LH was detected in stromal cells after 6 h of incubation (P< 0.001). Epithelial cells responded to LH after a longer exposure time (P< 0.01). A concentration-dependent effect of LH (0.1–100 ng/ml) on PGF2αrelease from stromal cells was examined after 6 h and from epithelial cells after 12 h (experiment 2). Effective concentrations of LH were 10 and 100 ng/ml. LH (10 ng/ml) and oxytocin (100 nmol/l) affected PGF2αand PGE2secretion from endometrial cells on days 10–12 and 14–16 of the oestrous cycle (experiment 3). LH stimulated PGF2αsecretion from both cell types and its action was more potent on days 10–12. LH induced PGE2release, especially in epithelial cells on days 14–16. A stimulatory effect of oxytocin on PGF2αwas confirmed in stromal cells, but this hormone was also shown to enhance PGE2output. These results indicated that LH, like oxytocin, a very effective stimulator of PGF2αrelease, could play an important role in the induction of luteolysis.
The Health of Poor Women Under Welfare Reform
Authors: Kaplan George A. , Siefert Kristine , Ranjit Nalini , Raghunathan Trivellore E. , Young Elizabeth A. , Tran Diem , Danziger Sandra , Hudson Susan , Lynch John W. , Tolman Richard
Published: June 2005

Objectives. We compared the health of single mothers affected by welfare reform with the health of a nationally representative sample of women to document the prevalence of poor health as single mothers experience the effects of welfare reform.

Methods. We compared risk factors and measures of health among women randomly sampled from the welfare rolls with similar data from a nationally representative sample of women.

Results. Women in our welfare recipient sample had higher rates of elevated glycosylated hemoglobin (≥ 6%; prevalence ratio [PR]=4.87; 95% confidence interval [CI]=2.69, 7.04), hypertension (systole ≥ 140 or diastole ≥ 90; PR=2.36; 95% CI = 1.47, 3.24), high body mass index ( ≥ 30; PR = 1.78; 95% CI = 1.49, 2.08), and high-density lipoprotein cholesterol (≤ 35 mg/dL; PR=1.91; 95% CI=1.17, 2.65); lower peak expiratory flow; and less physical functioning. Current smoking rates were higher (PR = 1.85; 95% CI = 1.50, 2.19) and smoking cessation rates were lower (PR=0.62; 95% CI=0.37, 0.86) than in the national sample.

Conclusions. Current and former welfare recipients bear a substantial burden of illness. Further studies are necessary to interpret our findings of worsened health in the wake of welfare reform.
Childhood Socioeconomic Position, Educational Attainment, and Adult Cardiovascular Risk Factors: The Aberdeen Children of the 1950s Cohort Study
Authors: Lawlor Debbie A , Batty G. David , Morton Susan M.B. , Clark Heather , Macintyre Sally , Leon David A.
Published: June 2005

Objectives. We assessed the associations of childhood socioeconomic position with cardiovascular disease risk factors (smoking, binge alcohol drinking, and being overweight) and examined the roles of educational attainment and cognitive functioning in these associations.

Methods. Data were derived from a cohort study involving 7184 individuals who were born in Aberdeen, Scotland, between 1950 and 1956; had detailed records on perinatal characteristics, childhood anthropometry, and cognitive functioning; and responded to a mailed questionnaire when they were aged 45 to 52 years.

Results. Strong graded associations existed between social class at birth and smoking, binge drinking, and being overweight. Adjustment for educational attainment completely attenuated these associations. However, after control for adult social class, adult income and other potential confounding or mediating factors, some association remained.

Conclusions. Educational attainment is an important mediating factor in the relation between socioeconomic adversity in childhood and smoking, binge drinking, and being overweight in adulthood.
Staffing and Worker Injury in Nursing Homes
Authors: Trinkoff Alison M. , Johantgen Meg , Muntaner Carles , Le Rong
Published: June 2005

Objectives. We examined the relationship between nursing home staffing levels and worker injury rates in 445 nursing homes in 3 states.

Methods. We obtained First Reports of Injury and workers’ compensation data from 3 states (Ohio, West Virginia, and Maryland) for the year 2000. We then linked these data to Medicare’s Online Survey, Certification and Reporting system to obtain nursing home staffing details and organizational descriptors. We used ordinary least squares and log-transformed regression models to examine the association between worker injury rate and nursing home staffing and organizational characteristics.

Results. Total nursing hours per resident day were significantly associated with worker injury rates in nursing homes after we adjusted for organizational characteristics and state dummy variables (P=.0004).

Conclusions. Our findings suggest that nursing home staffing levels have an important impact on worker health. These findings were supported for multiple facilities across different states; therefore, policies and resources that increase staffing levels in nursing homes are warranted.
Evaluation of the Cytochrome b5/Cytochrome b5 Reductase Pathway
Authors: Trepanier Lauren A. , Bajad Sunil U. , Kurian Joseph R.
Published: June 2005

NADH cytochrome b5 reductase (b5R; EC 1.6.2.2; Diaphorase I; NADH: ferricytochrome b5 oxidoreductase) is an FAD‐containing protein, which, along with the hemoprotein cytochrome b5 (cyt b5), mediates electron transfer from NADH to fatty acid desaturases, P450 oxidases, methemoglobin, and ascorbyl free radical. In addition, b5R and cyt b5 can directly catalyze the reduction of hydroxylamine and amidoxime metabolites. This unit provides protocols for measuring the activity and mRNA expression of the cytochrome b5/cytochrome b5 reductase pathway, and for obtaining heterologous expression and purification of the soluble forms of each protein.
Quantification of F2‐Isoprostanes by Gas Chromatography/Mass Spectrometry as a Measure of Oxidant Stress
Authors: Musiek Erik S. , Morrow Jason D.
Published: June 2005

Oxidative stress has been implicated in a wide variety of disease processes. One method to quantify oxidative injury is to measure lipid peroxidation. Most methods to do this are fraught with problems particularly when utilized to assess oxidative stress in vivo. On the other hand, quantification of a group of prostaglandin F2‐like compounds, termed the F2‐isoprostanes (F2‐IsoPs) provides an accurate assessment of oxidative stress both in vitro and in vivo and has come to be regarded as the gold standard to quantify lipid peroxidation. This unit describes methods to assess lipid peroxidation associated with oxidant injury in vivo by quantifying concentrations of either esterified or free F2‐IsoPs in biological fluids and tissues. The techniques employed for the analysis of these compounds from biological sources that are detailed herein utilize mass spectrometric approaches. Measurement of F2‐IsoPs represents an important advance in the ability to assess the role of oxidative stress in human disease.
Expanded‐Bed Adsorption Chromatography
Authors: Kennedy Robert M.
Published: June 2005

Expanded‐bed adsorption (EBA) chromatography is a convenient and effective technique for the capture of proteins directly from unclarified crude sample. In EBA chromatography, the settled bed is first expanded by upward flow of equilibration buffer. The crude feed, a mixture of soluble proteins, contaminants, cells, and cell debris, is then passed upward through the expanded bed. Target proteins are captured on the adsorbent, while particulates and contaminants pass through. A change to elution buffer while maintaining upward flow results in desorption of the target protein in expanded‐bed mode. Alternatively, if the flow is reversed, the adsorbed particles will quickly settle and the proteins can be desorbed by an elution buffer. The mode used for elution (expanded‐bed versus settled‐bed) depends on the characteristics of the feed. After elution, the adsorbent is cleaned with a predefined cleaning‐in‐place (CIP) solution, with cleaning followed by either column regeneration (for further use) or storage.
Impact characterization of a carbon fiber‐epoxy laminate using a nonconservative model
Authors: Martínez A. B. , Sánchez‐Soto M. , Velasco J. I. , Maspoch M. Ll. , Santana O. O. , Gordillo A.
Published: June 2005

The study of polymer and composite behavior under high strain rates is of fundamental relevance to determine the material suitability for a selected application. However, the impact phenomenon is a very complicated event, mainly due to the short duration, large deformation, and high stresses developed in the sample. In this work, we have performed impact tests over a carbon fiber reinforced epoxy using low‐energy in the striker. A nonconservative and nonlineal spring‐dashpot series model has been proposed to reproduce the material behavior. The model considers simultaneously both flexural and indentation phenomena accounting for energy losses by means of the restitution coefficient. Using this model, an excellent fit between the predicted and the experimental force‐time trace has been obtained below the composite failure point, which was recognized by a separation of both mentioned curves. As the epoxy‐fiber laminate has a very low viscoelasticity, the high strain rate Young's modulus obtained from the model was compared with that extracted from a conventional three point bending test, finding a very good match between the values. The study of the dashpot coefficients allows concluding that the dominant mechanism is the composite flexion, while the indentation effects contribution takes on importance at low impact velocities. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 97: 2256–2263, 2005
Isolation, cloning, and tissue expression of a putative octopamine/tyramine receptor from locust visceral muscle tissues
Authors: Molaei Goudarz , Paluzzi Jean‐Paul , Bendena William G. , Lange Angela B.
Published: June 2005

Octopamine has been shown to play major roles in invertebrate nervous systems as a neurotransmitter, neuromodulator, and neurohormone. Tyramine is the biochemical precursor of octopamine and its neuromodulatory role is now being investigated and clarified in invertebrates, particularly in insects. Both octopamine and tyramine mediate their actions via G protein‐coupled receptors (GPCRs) and are believed to play important functions in the regulation of physiological processes in locust oviduct. Here we report the isolation, cloning, and tissue expression of a putative octopamine/tyramine receptor from the locust, Locusta migratoria. Degenerate oligonucleotides in PCR reactions were first used to obtain partial cDNA sequences and then these partial sequences were used in screens to obtain a full‐length cDNA. The cloned cDNA is about 3.1 kb long and encodes a protein of 484 amino acid residues with typical characteristics of GPCRs including seven transmembrane domains and many signature residues. The amino acid sequence of the cloned cDNA displays sequence similarities with known GPCRs, particularly octopamine/tyramine receptors. Screening of the locust genomic DNA library resulted in isolation of a genomic DNA with the same size as the cDNA, indicating that the gene is intronless. RT‐PCR and Northern blot analyses revealed the expression of the receptor mRNA in brain, ventral nerve cord, oviduct, and midgut tissues. Southern blot analyses using EcoRI and HindIII restriction endonucleases recognized at least two distinct gene bands. Arch. Insect Biochem. Physiol. 59:132–149, 2005. © 2005 Wiley‐Liss, Inc.
Molecular and pharmacological analysis of an octopamine receptor from american cockroach and fruit fly in response to plant essential oils
Authors: Enan Essam E.
Published: June 2005

Octopamine receptors from American cockroach, Periplaneta americana (Pa oa1), and fruit fly, Drosophila melanogaster (OAMB), were cloned and permanently expressed in HEK‐293 cells, and found to activate adenylate cyclase activity and increase [Ca2+]i levels through G‐protein coupled receptor signaling pathways. Sequencing information (GenBank accession number AY333178) and functional data of Pa oa1 were recently published. Saturation binding analysis with 3H‐yohimbine was performed with Pa oa1 and OAMB expressed in COS‐7 cells. The Kd values were determined to be 28.4 and 43.0 nM, respectively. Bmax was determined to be 11.8 and 8.04 pmol receptor/mg protein, respectively. Competitive binding data using cell membranes expressing either OAMB or Pa oa1 demonstrated significantly decreased binding activity in binding assays performed in the presence of plant essential oils, eugenol, cinnamic alcohol, and trans‐anethole. Eugenol decreased cAMP level in HEK‐293 cells expressing Pa oa1, but trans‐anethole increased cAMP in HEK‐293 cells expressing OAMB. All three chemicals increased [Ca2+]i level in both cell models. Toxicity data against fruit flies and American cockroaches demonstrated species differences in response to treatment with tested plant essential oils. The toxicity of tested chemicals against wild type and octopamine mutant (iav) fly strains suggested that an octopamine receptor mediates the toxicity of cinnamic alcohol, eugenol, trans‐antehole, and 2‐phenethyl propionate against fruit flies. Collectively, the data suggest a correlation between cellular changes induced by tested plant essential oils and their toxicity against fruit fly and American cockroach. Arch. Insect Biochem. Physiol. 59:161–171, 2005. © 2005 Wiley‐Liss, Inc.
Damage caused by Wegener's granulomatosis and its treatment: Prospective data from the Wegener's Granulomatosis Etanercept Trial (WGET)
Authors: Seo Philip , Min Yuan‐I. , Holbrook Janet T. , Hoffman Gary S. , Merkel Peter A. , Spiera Robert , Davis John C. , Ytterberg Steven R. , St. Clair E. William , McCune W. Joseph , Specks Ulrich , Allen Nancy B. , Luqmani Raashid A. , Stone John H. ,   WGET Research Group
Published: June 2005

Objective

To analyze damage occurring in patients with Wegener's granulomatosis (WG) enrolled in the WG Etanercept Trial (WGET) and to correlate that damage with disease activity, adverse events, and quality of life.

Methods

The Vasculitis Damage Index (VDI) was applied to all 180 patients at trial entry and every 6 months throughout the trial. Items of damage were analyzed by presumed etiology (i.e., secondary to WG, to therapy, or both) and time of occurrence. Spearman's rank correlation coefficients were calculated between VDI scores and the Birmingham Vasculitis Activity Score for WG (BVAS/WG), frequency of flares, number of adverse events, and the patients' quality‐of‐life assessments.

Results

The mean VDI score was 1.3 at the study enrollment and 1.8 at the end of the trial. This increase was due to damage that occurred despite (or because of) therapy, including visual impairment, hearing loss, nasal blockade, pulmonary fibrosis, hypertension, renal insufficiency, peripheral neuropathy, gonadal failure, and diabetes mellitus. Only 11% of the enrolled patients had not sustained a single VDI item after 1 year of enrollment. When adjusted for baseline VDI, the baseline BVAS/WG correlated moderately well with the VDI score at 1 year (r = 0.20, P = 0.015). Increases in adjusted VDI scores also correlated with the number of adverse events, particularly among patients with limited WG (P = 0.06).

Conclusion

Damage from both active disease and its treatment remain important problems for patients with WG. Despite the dramatic improvements in patient survival achieved over the last several decades, only a few patients with WG emerge from a period of active disease without sustaining some damage from the disease itself, its treatment, or both. An important measure of future therapeutic approaches will be their ability to reduce the damage accrued over time.
Anti–tumor necrosis factor α blockade in the treatment of juvenile spondylarthropathy
Authors: Tse Shirley M. L. , Burgos‐Vargas Ruben , Laxer Ronald M.
Published: June 2005

Objective

Persistent inflammation refractory to standard antirheumatic therapy in children with juvenile spondylarthropathy (SpA) leads to morbidity and reduced quality of life. Tumor necrosis factor α (TNFα) plays an important role in the pathogenesis of synovitis and enthesitis. This study was undertaken to examine the impact of anti‐TNFα agents on juvenile SpA that is refractory to nonsteroidal antiinflammatory drugs (NSAIDs), disease‐modifying antirheumatic drugs, and corticosteroids.

Methods

Ten juvenile SpA patients with a mean ± SEM age of 15.0 ± 0.7 years and disease duration of 4.4 ± 0.8 years, all of whom were HLA–B27 positive, were followed up for 1 year after initiation of either infliximab (n = 8) or etanercept (n = 2). Outcomes examined were within‐subject differences in the tender entheseal count (TEC) and active joint count (AJC), markers of inflammation, functional assessments (Childhood Health Assessment Questionnaire [C‐HAQ] score), and requirements for antirheumatic drugs.

Results

At baseline, all patients exhibited active arthritis and enthesitis that were resistant to NSAIDs (n = 10), methotrexate (n = 6), sulfasalazine (n = 8), corticosteroids (oral n = 6, intravenous pulse n = 3, and intraarticular n = 6), and bisphosphonates (n = 2). In 2 patients, sulfasalazine (n = 2), corticosteroids (n = 1), and bisphosphonates (n = 1) were stopped after initiation of the anti‐TNFα agent. In all patients, the arthritis and enthesitis significantly improved as evidenced by remission of the TEC and AJC by 6 months that was sustained during the 1‐year followup, markers of inflammation and C‐HAQ scores normalized, and there was a reduction in requirements for antirheumatic drugs (reduced dosage or discontinuation of NSAIDs n = 10, methotrexate n = 5, sulfasalazine n = 6, corticosteroids n = 4, and bisphosphonates n = 1).

Conclusion

Anti‐TNFα therapy is a potential novel treatment for refractory juvenile SpA. Further prospective studies are required to examine the effectiveness and long‐term outcomes of anti‐TNFα therapy in this cohort.
Association of the lymphoid tyrosine phosphatase R620W variant with rheumatoid arthritis, but not Crohn's disease, in Canadian populations
Authors: Van Oene Mark , Wintle Richard F. , Liu Xiangdong , Yazdanpanah Mehrdad , Gu Xiangjun , Newman Bill , Kwan Albert , Johnson Benjamin , Owen Julie , Greer Wenda , Mosher Dianne , Maksymowych Walter , Keystone Ed , Rubin Laurence A. , Amos Christopher I. , Siminovitch Katherine A.
Published: June 2005

Objective

A single‐nucleotide polymorphism in the PTPN22 gene encoding the lymphoid protein tyrosine phosphatase (Lyp) has recently been identified as a functional variant associated with susceptibility to rheumatoid arthritis (RA), type 1 diabetes, and systemic lupus erythematosus. To determine whether association of this variant (PTPN22 1858T) with RA is reproducible and is also observed in another autoimmune condition, Crohn's disease, we investigated the association between the PTPN22 1858T allele and RA and Crohn's disease in a Canadian population.

Methods

Two RA case–control cohorts representing a total of 1,234 patients and 791 healthy controls as well as a cohort of 455 patients with Crohn's disease and 190 controls were genotyped for the PTPN22 C1858T polymorphism, and genotype frequencies were compared between patients and controls.

Results

Significant association of the PTPN22 1858T allele with RA was detected in both the Toronto‐based RA cohort (P = 1.6 × 10−6, odds ratio [OR] 1.8) and the Halifax‐based RA cohort (P = 9.4 × 10−4, OR 1.94). Association of the risk allele with RA was not affected by sex, age at disease onset, or the presence of either rheumatoid factor or rheumatoid nodules. No association between the PTPN22 risk allele and Crohn's disease was detected.

Conclusion

These observations confirm the association of RA susceptibility with the PTPN22 1858T allele. However, the data also reveal a lack of association between this variant and Crohn's disease, suggesting that the PTPN22 1858T allele is a risk allele for multiple, but not all, autoimmune diseases.
Systemic lupus erythematosus in a multiethnic US cohort (LUMINA): XXV. Smoking, older age, disease activity, lupus anticoagulant, and glucocorticoid dose as risk factors for the occurrence of venous thrombosis in lupus patients
Authors: Calvo‐Alén Jaime , Toloza Sergio M. A. , Fernández Mónica , Bastian Holly M. , Fessler Barri J. , Roseman Jeffrey M. , McGwin Gerald , Vilá Luis M. , Reveille John D. , Alarcón Graciela S. ,   LUMINA Study Group
Published: June 2005

Objective

Venous thrombosis is a relatively frequent and serious complication in systemic lupus erythematosus (SLE) that has been associated with the presence of antiphospholipid antibodies (aPL). However, venous thrombotic events can also be seen in patients without aPL, and only a few patients with aPL develop venous thrombosis. This study was carried out to ascertain other factors contributing to the development of venous thrombosis in SLE.

Methods

Patients with SLE, ages ≥16 years with ≤5 years disease duration and of Hispanic, African American, or Caucasian ethnicity, from LUMINA (LUpus in MInorities, NAture versus nurture), a multiethnic, longitudinal study of outcome, were studied. Selected socioeconomic/demographic, clinical, laboratory, and treatment‐exposure variables were compared between patients who developed and those who did not develop venous thrombotic events. Significant and clinically relevant variables were then entered into different multivariable models (Cox proportional hazards and unconditional stepwise logistic regression) to identify independent risk factors associated with the primary outcome. In another model, only patients who developed an event after enrollment (time 0) in the cohort were included.

Results

Of 570 LUMINA patients, 51 developed at least 1 venous thrombotic event after SLE diagnosis. In univariable analyses, smoking (P = 0.020), shorter disease duration at time 0 (P = 0.017), serum levels of total cholesterol, low‐density lipoprotein, and triglycerides (all P < 0.0001), and presence of lupus anticoagulant (LAC) (P = 0.045) were associated with venous thrombotic events. Survival analyses showed a time‐dependent significant association of the primary outcome with smoking (P = 0.008) and a borderline significant association with the presence of LAC (P = 0.070). Multivariable models showed an independent association with smoking, age at time 0, disease activity over time, LAC, mean dose of glucocorticoids, and shorter disease duration at time 0.

Conclusion

Venous thrombotic events occur early in the course of SLE. Our data confirm the association between LAC and venous thrombotic events. Smoking, shorter disease duration, older age, disease activity over time, and higher mean daily glucocorticoid dose were identified as additional risk factors for the development of this vascular complication. These findings may have implications for the management of patients with SLE.
Molecular Recognition of Aminoglycoside Antibiotics by Bacterial Defence Proteins: NMR Study of the Structural and Conformational Features of Streptomycin Inactivation by Bacillus subtilis Aminoglycoside‐6‐adenyl Transferase
Authors: Corzana Francisco , Cuesta Igor , Bastida Agatha , Hidalgo Ana , Latorre Montserrat , González Carlos , García‐Junceda Eduardo , Jiménez‐Barbero Jesús , Asensio Juan Luis.
Published: June 2005

The molecular recognition of streptomycin by Bacillus subtilis aminoglycoside‐6‐adenyl transferase has been analysed by a combination of NMR techniques and molecular dynamic simulations. This protein inactivates streptomycin by transferring an adenyl group to position six of the streptidine moiety. Our combined approach provides valuable information about the bioactive conformation for both the antibiotic and ATP and shows that the molecular recognition process for streptomycin involves a conformational selection phenomenon. The binding epitope for both ligands has also been analysed by 1D‐STD experiments. Finally, the specificity of the recognition process with respect to the aminoglycoside and to the nucleotide has been studied.
Absolute Asymmetric Synthesis of Stereochemically Labile Aldehyde Helicates and Subsequent Chirality Transfer Reactions
Authors: Johansson Anna , Håkansson Mikael
Published: June 2005

Helical complexes formed between aluminum tris(2,6‐diphenylphenoxide) (ATPH) and five different aldehydes have been prepared and structurally characterized by X‐ray diffraction. It was found that [Al(OC6H3Ph2)3PhCHO] (2), [Al(OC6H3Ph2)3(4‐CH3C6H4CHO)] (3), [Al(OC6H3Ph2)3(4‐tBuC6H4CHO)] (4), and [Al(OC6H3Ph2)3(p‐CH3OC6H4CHO)] (5) all crystallize as conglomerates, while crystals of [Al(OC6H3Ph2)3(o‐CH3OC6H4CHO)] (6) are racemic. Supramolecular CH/π interactions between molecules in crystals of 2–5 that enable stereochemical information to be mediated in three dimensions have been identified and explain the high frequency of conglomerate formation among ATPH helicates. Since 2–5 are stereochemically labile and thus enantiomerize rapidly in solution, the conglomerates can be resolved by crystallization‐induced asymmetric transformation. The determination of the enantiomeric excess (ee) in solid samples of stereochemically labile molecules is not trivial, but solid‐state CD spectroscopic data, anomalous dispersion data, and the ee values in alkylation reactions all indicate that preferential crystallization of 2–5 yields an essentially enantiopure product. Thus the preparation of 2–5 constitute new examples of absolute asymmetric synthesis. The helical chirality can be transferred (and thus trapped) to alcohols (with ee values of up to 16 %) in crystal‐to‐crystal reactions with achiral organometallic reagents.
Chicken gizzard filamin, retina filamin and cgABP260 are respectively, smooth muscle‐, non‐muscle‐ and pan‐muscle‐type isoforms: Distribution and localization in muscles
Authors: Ohashi Kazuyo , Oshima Koji , Tachikawa Masaji , Morikawa Nao , Hashimoto Yousuke , Ito Masayo , Mori Hajime , Kuribayashi Tomoko , Terasaki Asako G.
Published: June 2005

We determined the full cDNA sequences of chicken gizzard filamin and cgABP260 (chicken gizzard actin‐binding protein 260). The primary and secondary structures predicted by these sequences were similar to those of chicken retina filamin and human filamins. Like mammals, chickens have 3 filamin isoforms. Comparison of their amino acid sequences indicated that gizzard filamin, retina filamin, and cgABP260 were the counterparts of human FLNa (filamin a), b, and c, respectively. Antibodies against the actin‐binding domain (ABD) of these 3 filamin isoforms were raised in rabbits. Using immunoabsorption and affinity chromatography, we prepared the monospecific antibody against the ABD of each filamin. In immunoblotting, the antibody against the gizzard filamin ABD detected a single band in gizzard, but not in striated muscles or brain. In brain, only the antibody against the retina filamin ABD produced a strong single band. The antibody against the cgABP260 ABD detected a single peptide band in smooth, skeletal, and cardiac muscle. In immunofluorescence microscopy of muscular tissues using these antibodies, the antibody against the gizzard filamin ABD only stained smooth muscle cells, and the antibody against the retina filamin ABD strongly stained endothelial cells of blood vessels and weakly stained cells in connective tissue. The antibody against the cgABP260 ABD stained the Z‐lines and myotendinous junctions of breast muscle, the Z‐lines and intercalated disks of cardiac muscle, and dense plaques of smooth muscle. These findings indicate that chicken gizzard filamin, retina filamin, and cgABP260 are, respectively, smooth muscle‐type, non‐muscle‐type, and pan‐muscle‐type filamin isoforms. Cell Motil. Cytoskeleton 61:214–225, 2005. © 2005 Wiley‐Liss, Inc.
High‐dose‐rate brachytherapy as part of a multidisciplinary treatment of nasopharyngeal lymphoepithelioma in childhood
Authors: Nakamura Ricardo Akiyoshi , Novaes Paulo Eduardo Ribeiro dos Santos , Antoneli Célia Beatriz Gianotti , Fogaroli Ricardo César , Pellizzon Antonio Cássio Assis , Ferrigno Robson , Maia Maria Aparecida Conte , Salvajoli João Victor , Pereira Adelino José , Nishimoto Inês Nobuko
Published: June 2005

BACKGROUND

Nasopharyngeal carcinoma in childhood is rare. Radiochemotherapy is considered the standard treatment and yields increased survival and local control rates. In this article, the authors report on the results from the multidisciplinary treatment of pediatric patients who had nasopharyngeal lymphoepithelioma with radiochemotherapy, including high‐dose‐rate brachytherapy of the primary tumor site.

METHODS

Between May 1992 and May 2000, 16 children with nasopharyngeal lymphoepithelioma received neoadjuvant chemotherapy, conventional external beam radiotherapy, high‐dose‐rate brachytherapy, and adjuvant chemotherapy. Patients ranged in age from 7 years to 18 years, and 9 patients were male. Patient distribution according to clinical disease stage was as follows: Stage III, 1 patient; Stage IVA, 5 patients; Stage IVB, 9 patients; and Stage IVC, 1 patient. Three cycles of neoadjuvant and adjuvant chemotherapy in 3‐week intervals were administered with cyclophosphamide, vincristine, doxorubicin, and cisplatin. The median doses of external beam radiotherapy to the primary tumor, positive lymph nodes, and subclinical areas of disease were 55 grays (Gy), 55 Gy, and 45 Gy, respectively. Children received 2 insertions of high‐dose‐rate brachytherapy at 5 Gy per insertion: These were performed with metallic applicators inserted through the transnasal access under local anesthesia.

RESULTS

The median of follow‐up was 54 months. At the time of last follow‐up, 13 patients were alive without disease, 2 patients had died of disease, and 1 patient had died of treatment‐related cardiac failure. Local control was achieved in 15 of 16 patients. Chemotherapy‐related and radiotherapy‐related acute toxicity was relevant but tolerable.

CONCLUSIONS

In the current study, it was shown that the treatment was effective in the control of both local and distant disease, although there was relevant acute and late toxicity. High‐dose‐rate brachytherapy was deliverable on an outpatient basis with local anesthesia. Close follow‐up of these patients was necessary to evaluate the significance of treatment‐related late effects and their impact on quality of life. Cancer 2005. © 2005 American Cancer Society.
Phase II study of tariquidar, a selective P‐glycoprotein inhibitor, in patients with chemotherapy‐resistant, advanced breast carcinoma
Authors: Pusztai Lajos , Wagner Peter , Ibrahim Nuhad , Rivera Edgardo , Theriault Richard , Booser Daniel , Symmans Fraser W. , Wong Franklin , Blumenschein George , Fleming Donald R. , Rouzier Roman , Boniface Graeme , Hortobagyi Gabriel N.
Published: June 2005

BACKGROUND

The primary objective of this study was to determine whether addition of the selective P‐glycoprotein (P‐gp) inhibitor tariquidar (XR9576) to chemotherapy could induce an objective tumor response in patients who previously were resistant to the same agents. The secondary objectives were to evaluate P‐gp expression by immunohistochemistry (IHC), to determine functional activity of the P‐gp transporter before and after administration of tariquidar with serial technetium‐99m (99mTc)‐sestamibi scans, and to correlate those parameters with clinical response.

METHODS

Seventeen women with Stage III–IV breast carcinoma were included in the study who progressed (n = 13 women) or had stable disease (n = 4 women) on doxorubicin‐containing or taxane‐containing chemotherapy regimens. During the study, the same chemotherapy was continued without dose modifications, but tariquidar (150 mg intravenously) was added to the treatment regimen.

RESULTS

Thirty‐six percent of patients had P‐gp‐positive tumors by IHC, and 5 patients (29%) experienced increases ≥ 10% in sestamibi uptake (median increase, 40%; range, 10–63%) after the administration of tariquidar. There was one partial response in a patient who had the greatest increase in sestamibi uptake and who also showed inducible P‐gp expression. There was one patient who experienced severe doxorubicin/docetaxel‐related toxicity after tariquidar was added to her chemotherapy regimen.

CONCLUSIONS

Tariquidar showed limited clinical activity to restore sensitivity to anthracycline or taxane chemotherapy. Functional imaging of the tumor with 99mTc‐sestamibi scans before and after administration of multidrug‐resistance inhibitor may be useful to identify the small subset of patients who could benefit from multidrug‐resistance modulation in future trials. Cancer 2005. © 2005 American Cancer Society.
Differential distribution of release‐related proteins in the hippocampal CA3 area as revealed by freeze‐fracture replica labeling
Authors: Hagiwara Akari , Fukazawa Yugo , Deguchi‐Tawarada Maki , Ohtsuka Toshihisa , Shigemoto Ryuichi
Published: June 2005

Synaptic vesicle release occurs at a specialized membrane domain known as the presynaptic active zone (AZ). Several membrane proteins are involved in the vesicle release processes such as docking, priming, and exocytotic fusion. Cytomatrix at the active zone (CAZ) proteins are structural components of the AZ and are highly concentrated in it. Localization of other release‐related proteins including target soluble N‐ethylmaleimide‐sensitive‐factor attachment protein receptor (t‐SNARE) proteins, however, has not been well demonstrated in the AZ. Here, we used sodium dodecyl sulfate‐digested freeze‐fracture replica labeling (SDS‐FRL) to analyze quantitatively the distribution of CAZ and t‐SNARE proteins in the hippocampal CA3 area. The AZ in replicated membrane was identified by immunolabeling for CAZ proteins (CAZ‐associated structural protein [CAST] and Bassoon). Clusters of immunogold particles for these proteins were found on the P‐face of presynaptic terminals of the mossy fiber and associational/commissural (A/C) fiber. Co‐labeling with CAST revealed distribution of the t‐SNARE proteins syntaxin and synaptosomal‐associated protein of 25 kDa (SNAP‐25) in the AZ as well as in the extrasynaptic membrane surrounding the AZ (SZ). Quantitative analysis demonstrated that the density of immunoparticles for CAST in the AZ was more than 100 times higher than in the SZ, whereas that for syntaxin and SNAP‐25 was not significantly different between the AZ and SZ in both the A/C and mossy fiber terminals. These results support the involvement of the t‐SNARE proteins in exocytotic fusion in the AZ and the role of CAST in specialization of the membrane domain for the AZ. J. Comp. Neurol. 489:195–216, 2005. © 2005 Wiley‐Liss, Inc.
Complex colony‐level organization of the deep‐sea siphonophore Bargmannia elongata (Cnidaria, Hydrozoa) is directionally asymmetric and arises by the subdivision of pro‐buds
Authors: Dunn Casey W.
Published: June 2005

Siphonophores are free‐swimming colonial hydrozoans (Cnidaria) composed of asexually produced multicellular zooids. These zooids, which are homologous to solitary animals, are functionally specialized and arranged in complex species‐specific patterns. The coloniality of siphonophores provides an opportunity to study the major transitions in evolution that give rise to new levels of biological organization, but siphonophores are poorly known because they are fragile and live in the open ocean. The organization and development of the deep‐sea siphonophore Bargmannia elongata is described here using specimens collected with a remotely operated underwater vehicle. Each bud gives rise to a precise, directionally asymmetric sequence of zooids through a stereotypical series of subdivisions, rather than to a single zooid as in most other hydrozoans. This initial description of development in a deep‐sea siphonophore provides an example of how precise colony‐level organization can arise, and illustrates that the morphological complexity of cnidarians is greater than is often assumed. Developmental Dynamics 234:835–845, 2005. © 2005 Wiley‐Liss, Inc.
Synthesis of New 3H‐Pyrazoles and Cyclopropenyl Alcohols Directly from Propargyl Alcohols
Authors: Hamdi Naceur , Dixneuf Pierre H. , Khemiss Abdelkader
Published: June 2005

The 1,3‐dipolar cycloaddition of 2‐diazopropane (1) to propargylic alcohols is regioselective and leads to 3H‐pyrazoles 3 in good yield. The surprising formation of the tetrasubstituted 3H‐pyrazole 4c from HC≡CCH2OH and 1 can be explained by formation of an initial 1,3‐dipolar cycloadduct intermediate followed by a second cycloaddition of 1 to the C=C bond and loss of dinitrogen. Photolysis of the antibacterial 3H‐pyrazoles 3 and 4 selectively gives α‐ and β‐dimethylcyclopropenyl alcohols 5 and 6, respectively. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Computational Study of Chronoamperometry at Rectangular Microelectrodes
Authors: Strutwolf J.
Published: June 2005

Three (space) dimensional diffusion to a rectangular microelectrode of length l and width w, embedded in an infinite coplanar insulator is simulated with boundary conditions for a chronoamperometric experiment. An alternating direction implicit finite difference method (Douglas‐Gunn algorithm) utilizing a problem adapted grid is used to solve the diffusion equation. Current transients are computed for different values of the dimensionless length parameter L=l/w, starting with L=1, i.e., a square electrode. Edge effects at the four sides of the rectangular electrode as well as the vertex effect contribute to the total current. With increasing L the transients approach the behavior of a microband electrode transient, where diffusion is essentially two dimensional. The breakdown of the two dimensional diffusion approach with decreasing values of L is analyzed and quantified. This serves as a guideline for analyzing transients measured with electrodes where the condition l » w is not fulfilled.
Electrochemical Study of Catechol in the Presence of Dibuthylamine and Diethylamine in Aqueous Media: Part 1. Electrochemical Investigation
Authors: Kiani Abolfazl , Raoof Jahan‐Bakhsh , Nematollahi Davood , Ojani Reza
Published: June 2005

Electrochemical oxidation of catechol has been studied in the presence of secondary amines as nucleophiles in aqueous solution with various pH values using cyclic voltammetry and differential pulse voltammetry. Cyclic voltammetry of catechol in pure buffered solution (2.00$\rm{\le}$pH<9.00) shows one anodic and corresponding cathodic peak which relates to the transformation of catechol to corresponding o‐benzoquinone and vice versa within a quasi‐reversible two electron transfer process. Also, a little amount of o‐benzoquinone undergoes polymerization reaction. Cyclic voltammogram of catechol in the presence of nucleophilic amines, show one anodic peak in the first scan of potential but on the reverse scan the corresponding cathodic peak disappear and new peak is observed at less positive potential. In the second scan of potential also a new anodic peak is observed. On the other hand at high concentration of amines the redox peak attributable to formed polymer disappear showing that in this condition the polymerization reaction occurs at non‐measurable extent. On the basis of these observations we propose an ECE mechanism for the electrochemical oxidation of catechol in the presence of secondary amines.
Protein phosphatase activity of PTEN inhibited the invasion of glioma cells with epidermal growth factor receptor mutation type III expression
Authors: Cai Xiu‐Mei , Tao Bei‐Bei , Wang Li‐Ying , Liang Yu‐Long , Jin Jia‐Wei , Yang Yong , Hu Ya‐Li , Zha Xi‐Liang
Published: June 2005

PTEN is a major tumor suppressor gene that has been shown to inhibit cell invasion. Its mutation has been found in 20–40% of malignant gliomas. Meanwhile, the type III EGFR mutation (EGFRvIII), which was frequently found in gliomas, promoted cell invasion. In the present study, the effects of PTEN on cell invasion were investigated in U87ΔEGFR glioblastoma cells with EGFRvIII expression but missing PTEN. The cell invasion was downregulated by transfection of phosphatase‐active forms of PTEN (wild‐type and G129E) but not by PTEN (C124A) with an inactive phosphatase domain; the effects were correlated with decreased tyrosine phosphatase levels of FAK at Tyr397, which was increased by EGFRvIII. Overexpression of FAK mutant (Y397F) could partially mimic the effect of PTEN on cell invasion. Although EGFRvIII increased the levels of P‐Akt and PTEN eliminated it, PI‐3K inhibitors, wortmannin or Ly294002, could not decrease the cell invasion. In conclusion, PTEN could inhibit cell invasion even in the presence of the constitutively active EGFR; this inhibition depended on its protein phosphatase activity, partially by dephosphorylating FAK, but not depended on its lipid phosphatase activity. © 2005 Wiley‐Liss, Inc.