bluuebunny/crossref_metadata_2025 huggingface dataset:
Thrombomodulin: An overview and potential implications in vascular disorders
Authors: Boffa M-C , Karmochkine M
Published: March 2009

Thrombomodulin (TM), a high affinity thrombin receptor present on endothelial cell membrane, plays an important role as a natural anticoagulant. It acts as a cofactor of thrombin-catalyzed activation of protein C, and inhibits the procoagulant functions of thrombin. TM is also located in other cells (keratinocytes, osteoblasts, macrophages, …) where it might be involved in cell differentiation or in inflammation. In the presence of cytokines, activated neutrophils and macrophages, endothelial TM is cleaved enzymatically, releasing soluble fragments which circulate in the blood and are eliminated in urine. Plasma TM level (pTM) can be measured using a two-site enzyme-linked immunosorbent assay (ELISA). pTM level is regarded as a molecular marker reflecting injury of endothelial cells. It is often increased in case of diffuse endothelial damage as in disseminated intravascular coagulation, diabetic microangiopathy, Plasmodium falciparum and rickettsial infections. pTM is also a predictive marker of hypertensive complications in pregnancy. In several systemic inflammatory diseases, pTM levels are correlated to the activity of the disease.
Antiphospholipid antibodies and atherosclerosis
Authors: Matsuura E , Kobayashi K , Yasuda T , Koike T
Published: March 2009

β2-Glycoprotein I (β2-GPI) is a major antigen for anticardiolipin antibodies (aCL) induced in patients with antiphospholipid syndrome and their antigenic epitopes are cryptic. The epitopes appear on the surface of β2-GPI molecule only when β2-GPI interacts with lipid membranes containing negatively charged phospholipids or polyoxygenated polystyrene surface. Our data also indicated that CuSO4-oxidized low density lipoproteins (oxLDL) are subsequently targeted by β2-GPI and aCL; however, malonedialdehyde (MDA)-modified LDL were recognized neither by β2-GPI nor aCL. β2-GPI binding to LDL was rapidly increased by incubation with CuSO4. Oxidation of lipoproteins was accompanied with the increment of thiobarbituric acid-reactive substances (TBARS) and denature of apolipoprotein. Ligands on LDL for β2-GPI seemed to be intermediate oxidative derivatives which were extractable into the chloroform phase by Bligh and Dyer's extraction, but not MDA. Further, immune responses against β2-GPI, as an anti-atherogenic protein, were demonstrated to induce atherogenic effect in in vitro oxLDL uptake by macrophages.
Atherosclerosis and the antiphospholipid syndrome: A link unravelled?
Authors: Shoenfeld Y , Harats D , George J
Published: March 2009

Atherosclerosis is a multifactorial disease that involves the arterial system. Recent data suggest that immune and autoimmune factors play a dominant role in mediating the progression of atherosclerosis. Among these factors, humoral response to modified forms of LDL and heat-shock proteins has been shown to be influential.

The antiphospholipid syndrome (APS) entails clinical manifestations that result from a hypercoagulable state. Antibodies to phospholipids and to β2-glycoprotein I have been suggested to confer the tendency to thrombosis. In a set of recent studies, we have been able to show that generation of antiphospholipid antibodies in mice is associated with enhanced atherosclerosis. These findings imply that APS and atherosclerosis may share a common etiologic background, which may have direct implications for the management of both conditions.
Development and Validation of the Evidence-Based Practice Process Assessment Scale: Preliminary Findings
Authors: Rubin Allen , Parrish Danielle E.
Published: March 2009

Objective: This report describes the development and preliminary findings regarding the reliability, validity, and sensitivity of a scale that has been developed to assess practitioners’ perceived familiarity with, attitudes about, and implementation of the phases of the evidence-based practice (EBP) process. Method: After a panel of national experts on EBP supported the scale’s content validity, social workers were surveyed by mail in Texas and Missouri to assess the scale’s internal consistency reliability and criterion validity. Additional data on the scale’s criterion validity and sensitivity were gathered in pretests and posttests of social workers participating in EBP continuing education workshops in Austin and San Antonio, Texas. Results: Preliminary findings support the scale’s internal consistency reliability, criterion validity, and sensitivity. Conclusion: In light of the current need and requests for this scale, dissemination of the preliminary findings is warranted while awaiting data collection at additional sites. These findings support the use of the scale to evaluate current efforts to educate students and practitioners in EBP.
Conceptual and Technical Issues Regarding the Use of HEDIS and HEDIS-Like Measures in Preferred Provider Organizations
Authors: Kleinman Lawrence C.
Published: March 2009

Preferred provider organizations (PPOs) represent a diverse and complex set of arrangements among insurance entities, networks of physicians, network organizers, and purchasers. Opinions differ regarding the degree to which PPOs have responsibility to manage care and to measure and report key aspects of their performance to customers and the public. Technical and operational challenges to performance measurement currently limit public reporting, even when agreement exists that it is appropriate for PPOs to do so. The Health Plan and Employer Data and Information Set (HEDIS) is a health maintenance organization performance measure that could provide standards for PPO reporting. This article explores conceptual and methodological considerations regarding HEDIS and other performance measurement in PPOs and identifies failures of the current marketplace. While using some measures may be premature or inappropriate, there are significant opportunities to apply other measures now and, by doing so, to create a functional health care marketplace.
Compassionate Care
Authors: Burnell Lori
Published: March 2009

Compassion may be nursing's most precious asset, yet the concept of compassion (or compassionate care) remains notably absent from nursing scholarship and the practicalities related to contemporary care delivery models. The provision of compassionate care is more than a professional mandate or an attribute of a model expressed in theoretical terms; it is the result of an authentic bond between a nurse and a patient. A concept analysis using Walker and Avant's methodology is employed using compassionate care as the virtue that allows a nurse to enter into the pain, suffering, and adversities a patient experiences as a way of establishing a meaningful connection.
Randomized, double-blind, placebo-controlled study of subcutaneous interferon beta-Ia in relapsing-remitting multiple sclerosis: a categorical disability trend analysis
Authors: Liu C. , Blumhardt LD
Published: March 2009

The treatment effects of recent immunomodulatory therapies on disease progression in relapsing-remitting multiple sclerosis (MS) have been mostly established from 'confirmed progression' endpoints. However, the reliability of this outcome measure is poor and a significant proportion of patients may be erroneously classified. We previously proposed the area under disability/time curves to quantify in-trial disability changes, but although these have advantages, they lack information on the direction of change. We have therefore performed disease trend analyses and categorical classifications using serial Expanded Disability Status Scale (EDSS) scores from the 533 complete datasets in a double-blind, randomized, placebo-controlled, phase III trial of subcutaneous interferon β-1a (IFNβ-1a) (PRISMS study). We found significant treatment benefits for IFNβ-1a on in-trial disability course (P=0.002). Therapeutic advantages remained when relapse-related assessments were excluded (P=0.018). Post hoc analyses demonstrated that IFNβ-la was mainly effective in both increasing the proportion of patients with a 'stable' course and reducing those with prolonged, disabling deteriorations. Baseline disease duration and EDSS levels, but not MRI lesion load, predicted the subsequent disability trends. Mean 'numbers needed to treat' (NNTs) to obtain preferred disability courses were reduced in patients with shorter disease duration. These results have important implications for the targeting of immunomodulatory therapies in MS. Multiple Sclerosis (2002) 8, 10-14
A double-blind pilot study of the effect of Prokarin™ on fatigue in multiple sclerosis
Authors: Gillson G. , Richards TL , Smith RB , Wright JV
Published: March 2009

In this 12-week study with 29 subjects, the effect of Prokarin™ (n =22), a proprietary blend of histamine and caffeine, was compared to placebo group (n=7) for the following outcomes: 1) fatigue as measured by the Modified Fatigue Impact Scale (MFIS); 2) lower limb function as measured by timed walk test; 3) upper limb function as measured by the pegboard test; 4) cognitive function as measured by the Paced Auditory Serial Additions Test (PASAT); 5) serum caffeine level; 6) change in brain chemistry as measured by quantitative magnetic resonance spectroscopy assay of N-acetyl aspartate (NAA); and 7) safety as measured by routine blood chemistry, TSH and urinalysis. Data were acquired at baseline, 4, 8 and 12 weeks. The Prokarin™ group MFIS mean was significantly different from the mean of the placebo group at 12 weeks (df=24, t=2.08, P=<0.02), with respective means of 37.40, SD=15.18, for the Prokarin™ group and 53.2, SD=11.39 for the controls. For the secondary endpoints (PASAT, 25 foot timed walk, peg test, and magnetic resonance spectroscopy [MRS]), there were no significant differences between the Prokarin™-treated group and the placebo group. However, there were significant improvements within the Prokarin™ group for each of these measures for the pre- versus posttreatment comparison at 12 weeks. Serum caffeine data indicated that caffeine exerted no independent effect on performance. No laboratory abnormalities were seen, and the treatment was well tolerated. Conclusion: There was a modest-size statistical effect of Prokarin ™ on fatigue in multiple sclerosis (MS) compared with the placebo group. A larger trial is warranted, based on this pilot study. Multiple Sclerosis (2002) 8, 30-35
High clinical inflammatory activity prior to the development of secondary progression: a prospective 5-year follow-up study
Authors: Casanova B. , Coret F. , Valero C. , Landete L. , Pascual A. , Vilchez JJ
Published: March 2009

Objective: To study if there are different patterns of clinical activity - measured by the annual exacerbation rate (AER) - among relapsing-remitting multiple sclerosis (RRMS), "early" secondary multiple sclerosis (SPMS) and "late" SPMS. Methods: A prospective 5-year follow-up study in 80 MS patients has been carried out, calculating the AER and the mean expanded disability status scale (EDSS) change rate (MCR). Results: A significant difference on the AER, among RRMS, early SPMS and late SPMS, has been found. Conclusions: The SPMS has a high clinical inflammatory activity before and during its transformation from a RRMS. Multiple Sclerosis (2002) 8, 59-63
Endogenous production of nitric oxide synthase inhibitors
Authors: Anthony Shelagh , Leiper James , Vallance Patrick
Published: March 2009

Numerous reports have indicated that the plasma concentration of endogenously produced inhibitors of nitric oxide synthase are elevated in human disease states. In this review we discuss recent advances in our understanding of the enzymes responsible for the synthesis of these inhibitors.
DDAH gene and cardiovascular risk
Authors: Valkonen Veli-Pekka , Tuomainen Tomi-Pekka , Laaksonen Reijo
Published: March 2009

The crucial role of nitric oxide (NO) for normal endothelial function is well known. In many conditions associated with increased risk of cardiovascular diseases such as hypercholesterolemia, hypertension, abdominal obesity, diabetes and smok ing, NO biosynthesis is dysregulated, leading to endothelial dysfunction. The grow ing evidence from animal and human studies indicates that endogenous inhibitors of endothelial NO synthase such as asymmetric dimethylarginine (ADMA) and NG-monomethyl-L-arginine (L-NMMA) are associated with the endothelial dysfunc tion and potentially regulate NO synthase. The major route of elimination of ADMA is metabolism by the enzymes dimethylarginine dimethylaminohydrolase-1 and -2 (DDAH). In our recent study 16 men with either low or high plasma ADMA concen trations were screened to identify DDAH polymorphisms that could potentially be associated with increased susceptibility to cardiovascular diseases. In that study a novel functional mutation of DDAH-1 was identified; the mutation carriers had a significantly elevated risk for cardiovascular disease and a tendency to develop hypertension. These results confirmed the clinical role of DDAH enzymes in ADMA metabolism. Furthermore, it is possible that more common variants of DDAH genes contribute more widely to increased cardiovascular risk.
Quantification of ADMA: analytical approaches
Authors: Schwedhelm Edzard
Published: March 2009

Methylated L-arginine analogs are involved in nitric oxide synthase activity regulation. Methods based on high-performance liquid chromatography with fluorescence, capillary electrophoresis, or ion exchange chromatography with absorbance detection were first applied for the quantitative determination of N-monomethyl-L-arginine (NMMA), asymmetric dimethylarginine (ADMA) and sym metric dimethylarginine (SDMA) in human blood and urine. These assays revealed elevated circulating levels of ADMA in various diseases and gave accumulating evidence of the usefulness of ADMA as a cardiovascular risk factor. However, the methods used are hampered by the fact that NMMA, ADMA and SDMA can be dis tinguished from L-arginine only by means of chromatographic separation. This has promoted the development of alternatives that involve mass spectrometry (MS) technology. Today, various MS-based approaches such as liquid chromatography (LC)-MS, LC-MS/MS, gas chromatography (GC)-MS, and GC-MS/MS are available. L-arginine and its analogs have been subjected to LC-MS analysis with and without further derivatization to their o-phthaldialdehyde derivatives. For these methods, labelled L-arginine was used as the internal standard. The first MS-based method that distinguishes NMMA, ADMA, SDMA and L-arginine by mass-to-charge (m/z)- ratio has been reported by Tsikas et al. This GC-MS approach has been further improved by Albsmeier et al by introducing labelled ADMA as an internal standard. As an alternative to existing methods, a commercially available ELISA kit has recently been developed and validated.
The Changing Meanings of Work in Germany
Authors: Borchert Margret , Landherr Gerrit
Published: March 2009

The problem and the solution. This article analyzes the changing meaning of work in Germany since the country's reunification in 1990.The theoretical frame of reference for this study is provided by the work of England and colleagues. On this basis, a number of published studies are evaluated and examined with regard to the hypothesis that the meaning of work in Germany is subject to a process change. Current results suggest that it is possible to identify various employees' “value types” and work preferences.The changing meaning of work is especially noticeable among the cohort of young academics and depends on varying labor market situations. Conjoint analysis is suggested to provide new insights into employees' values and preferences in the field of meaning of work.
Prevalence of HIV-1 Subtypes in Brazilian Children With Perinatally Acquired Infection
Authors: Molina Rosana M. , Torina Anali G. , Biffi Keila , Bismara Beatriz A. P. , Albuquerque Dulcineia M. , Andrade Paula D. , Anjos Emanuel B. V. , Toro Adleia D. C. , Nolasco Marcos T. , Vilela Maria M. S. , Costa Sandra C. B.
Published: March 2009

HIV-1 infection has increased among women in recent years. The HIV-1 env gene (structural gene) has the greatest variation in all the HIV gene regions. In this study, 58 samples from infants infected with HIV-1 via perinatal transmission were analyzed. All the 58 samples were submitted to Nested-polymerase chain reaction of the env gene region for posterior viral genotyping using EN 70 and EN 85 (first polymerase chain reaction) and EN 80 and EN 95 (second polymerase chain reaction) primers, with the product of the 682 base pair amplification. After Nested-polymerase chain reaction for genotyping, purification of the product, and direct sequencing in a MegaBace 1000 automatic sequencer, 56 genotypes were found in the 58 HIV-1-positive children of the study, where 47 (83.93%) were HIV-1 subtype B infected and 9 (16.07%) were HIV-1 subtype F1 infected. The results demonstrate the predominance of subtype B followed by subtype F in Southeast Brazil.
Relationship of Psychological Distress and Unprotected Sex Among Individuals With HIV Seeking Mental Health Care
Authors: Shacham Enbal , Basta Tania B. , Reece Michael
Published: March 2009

This study examined the prevalence of sexual behavior and its relationship with psychological distress among individuals with HIV who were seeking mental health care. Upon self-enrollment in HIV-related mental health care, 845 participants completed self-assessments of demographics, psychological distress, and sexual behaviors. Participants were categorized by sexual risk as determined by their reported unprotected sexual activity within the previous 30 days: receptive anal or vaginal sex (high-risk), insertive anal or vaginal sex (moderate-risk), oral sex (low-risk), and no sex (no-risk). The majority of the sample was classified as no-risk, 11% low-risk, 5% moderate-risk, and 17% were high-risk. Levels of psychological distress did not differ across risk levels. Overall psychological distress levels were elevated, 19% of the sample expressed severe distress. Use of illicit drugs, alcohol, and no-AIDS diagnosis predicted high-risk sexual behaviors. A substantial proportion of the sample reported engaging in high-risk sexual behaviors, which signifies the need to further incorporate sex-related prevention efforts among HIV-infected populations.
Upper Extremity Function in Persons with Tetraplegia: Relationships Between Strength, Capacity, and the Spinal Cord Independence Measure
Authors: Rudhe Claudia , van Hedel Hubertus J. A.
Published: March 2009

Objective. To quantify the relationship between the Spinal Cord Independence Measure III (SCIM III), arm and hand muscle strength, and hand function tests in persons with tetraplegia. Methods. A total of 29 individuals with tetraplegia (motor level between cervical 4 and thoracic 1; sensory-motor complete and incomplete) participated. The total score, category scores, and separate items of the SCIM III were compared to the upper extremity motor score (UEMS), an extended manual muscle test (MMT) for 11 upper extremity muscles, and 6 functional capacity tests of the hand. Spearman's correlation coefficients ( rs) and regression analyses were performed. Results. The SCIM III sum score correlated well with the sum scores of the 3 tests ( rs ≥ .76). The SCIM III self-care category correlated better with the tests ( rs ≥ .80) compared to the other categories ( r s ≤ .72). The SCIM III self-care item “grooming” highly correlated with muscle strength and hand capacity items ( rs ≥ .80). A combination of hand muscle tests and the key grasping task explained over 90% of the variability in the self-care category scores. Conclusions. The SCIM III self-care category reflects upper extremity performance as it contains especially useful and valid items that relate to upper extremity function and capacity tests.
Alterations of systemic and muscle iron metabolism in human subjects treated with low-dose recombinant erythropoietin
Authors: Robach Paul , Recalcati Stefania , Girelli Domenico , Gelfi Cecilia , Aachmann-Andersen Niels J. , Thomsen Jonas J. , Norgaard Anne M. , Alberghini Alessandra , Campostrini Natascia , Castagna Annalisa , Viganò Agnese , Santambrogio Paolo , Kempf Tibor , Wollert Kai C. , Moutereau Stéphane , Lundby Carsten , Cairo Gaetano
Published: March 2009

The high iron demand associated with enhanced erythropoiesis during high-altitude hypoxia leads to skeletal muscle iron mobilization and decrease in myoglobin protein levels. To investigate the effect of enhanced erythropoiesis on systemic and muscle iron metabolism under nonhypoxic conditions, 8 healthy volunteers were treated with recombinant erythropoietin (rhEpo) for 1 month. As expected, the treatment efficiently increased erythropoiesis and stimulated bone marrow iron use. It was also associated with a prompt and considerable decrease in urinary hepcidin and a slight transient increase in GDF-15. The increased iron use and reduced hepcidin levels suggested increased iron mobilization, but the treatment was associated with increased muscle iron and L ferritin levels. The muscle expression of transferrin receptor and ferroportin was up-regulated by rhEpo administration, whereas no appreciable change in myoglobin levels was observed, which suggests unaltered muscle oxygen homeostasis. In conclusion, under rhEpo stimulation, the changes in the expression of muscle iron proteins indicate the occurrence of skeletal muscle iron accumulation despite the remarkable hepcidin suppression that may be mediated by several factors, such as rhEpo or decreased transferrin saturation or both.
Neutrophils phagocytose activated platelets in vivo: a phosphatidylserine, P-selectin, and β2 integrin–dependent cell clearance program
Authors: Maugeri Norma , Rovere-Querini Patrizia , Evangelista Virgilio , Covino Cesare , Capobianco Annalisa , Bertilaccio Maria T. S. , Piccoli Antonio , Totani Licia , Cianflone Domenico , Maseri Attilio , Manfredi Angelo A.
Published: March 2009

Activated platelets express ligands, which are recognized by counterreceptors on neutrophils. Here, we show that the ensuing cell-to-cell interaction programs neutrophil phagocytic function, resulting in activated platelet clearance. Neutrophils that have internalized platelets circulate in the blood of patients with acute myocardial infarction, and the extent of platelet clearance correlates with expression of platelet activation, including P-selectin. Activated platelets injected intravenously in experimental animals are detectable in circulating neutrophils 60 minutes after, and within 3 hours, more than 70% circulating neutrophils have internalized platelets. Platelet clearance comprises 2 events: adhesion to neutrophils, which requires divalent cations and depends on P-selectin, on the P-selectin glycoprotein ligand-1 (PSGL-1), and on the CD11b/CD18 β2 integrin; and internalization, which is abrogated by the phosphatidylserine-binding protein annexin A5. Adhesion to platelets causes neutrophil degranulation and is blocked by antibodies specific for P-selectin and PSGL-1, either in a synthetic medium in vitro or in the whole blood, therefore in the presence of a physiologic array of plasma cofactors and opsonins. The data suggest that the interaction between circulating platelets and neutrophils influences innate immune functions, possibly contributing to regulate vascular inflammation.
Comparison of imatinib 400 mg and 800 mg daily in the front-line treatment of high-risk, Philadelphia-positive chronic myeloid leukemia: a European LeukemiaNet Study
Authors: Baccarani Michele , Rosti Gianantonio , Castagnetti Fausto , Haznedaroglu Ibrahim , Porkka Kimmo , Abruzzese Elisabetta , Alimena Giuliana , Ehrencrona Hans , Hjorth-Hansen Henrik , Kairisto Veli , Levato Luciano , Martinelli Giovanni , Nagler Arnon , Lanng Nielsen Johan , Ozbek Ugur , Palandri Francesca , Palmieri Fausto , Pane Fabrizio , Rege-Cambrin Giovanna , Russo Domenico , Specchia Giorgina , Testoni Nicoletta , Weiss-Bjerrum Ole , Saglio Giuseppe , Simonsson Bengt
Published: March 2009

Imatinib mesylate (IM), 400 mg daily, is the standard treatment of Philadelphia-positive (Ph+) chronic myeloid leukemia (CML). Preclinical data and results of single-arm studies raised the suggestion that better results could be achieved with a higher dose. To investigate whether the systematic use of a higher dose of IM could lead to better results, 216 patients with Ph+ CML at high risk (HR) according to the Sokal index were randomly assigned to receive IM 800 mg or 400 mg daily, as front-line therapy, for at least 1 year. The CCgR rate at 1 year was 64% and 58% for the high-dose arm and for the standard-dose arm, respectively (P = .435). No differences were detectable in the CgR at 3 and 6 months, in the molecular response rate at any time, as well as in the rate of other events. Twenty-four (94%) of 25 patients who could tolerate the full 800-mg dose achieved a CCgR, and only 4 (23%) of 17 patients who could tolerate less than 350 mg achieved a CCgR. This study does not support the extensive use of high-dose IM (800 mg daily) front-line in all CML HR patients. This trial was registered at www.clinicaltrials.gov as #NCT00514488.
R2* magnetic resonance imaging of the liver in patients with iron overload
Authors: Hankins Jane S. , McCarville M. Beth , Loeffler Ralf B. , Smeltzer Matthew P. , Onciu Mihaela , Hoffer Fredric A. , Li Chin-Shang , Wang Winfred C. , Ware Russell E. , Hillenbrand Claudia M.
Published: March 2009

R2* magnetic resonance imaging (R2*-MRI) can quantify hepatic iron content (HIC) by noninvasive means but is not fully investigated. Patients with iron overload completed 1.5T R2*-MRI examination and liver biopsy within 30 days. Forty-three patients (sickle cell anemia, n = 32; β-thalassemia major, n = 6; and bone marrow failure, n = 5) were analyzed: median age, 14 years, median transfusion duration, 15 months, average (±SD) serum ferritin 2718 plus or minus 1994 ng/mL, and average HIC 10.9 plus or minus 6.8 mg Fe/g dry weight liver. Regions of interest were drawn and analyzed by 3 independent reviewers with excellent agreement of their measurements (intraclass correlation coefficient = 0.98). Ferritin and R2*-MRI were weakly but significantly associated (range of correlation coefficients among the 3 reviewers, 0.41-0.48; all P < .01). R2*-MRI was strongly associated with HIC for all 3 reviewers (correlation coefficients, 0.96-0.98; all P < .001). This high correlation confirms prior reports, calibrates R2*-MRI measurements, and suggests its clinical utility for predicting HIC using R2*-MRI. This study was registered at www.clinicaltrials.gov as #NCT00675038.
Contrasting genetic association of IL2RAwith SLE and ANCA – associated vasculitis
Authors: Carr Edward J , Clatworthy Menna R , Lowe Christopher E , Todd John A , Wong Andrew , Vyse Timothy J , Kamesh Lavanya , Watts Richard A , Lyons Paul A , Smith Kenneth GC
Published: March 2009

Background

Autoimmune diseases are complex and have genetic and environmental susceptibility factors. The objective was to test the genetic association of systemic lupus erythematosus (SLE) and anti-neutrophil cytoplasmic antibody (ANCA) – associated systemic vasculitis (AAV) with SNPs in theIL2RAregion and to correlate genotype with serum levels of IL-2RA.

Methods

Using a cohort of over 700 AAV patients, two SLE case-control studies and an SLE trio collection (totalling over 1000 SLE patients), and a TaqMan genotyping approach, we tested 3 SNPs in the IL2RA locus, rs11594656, rs2104286 & rs41295061, each with a prior association with autoimmune disease; rs11594656 and rs41295061 with type 1 diabetes (T1D) and rs2104286 with multiple sclerosis (MS) and T1D.

Results

We show that SLE is associated with rs11594656 (P= 3.87 × 10-7) and there is some evidence of association of rs41295061 with AAV (P= 0.0122), which both have prior association with T1D. rs2104286, an MS and T1D – associated SNP in theIL2RAlocus, is not associated with either SLE or AAV.

Conclusion

We have confirmed a previous suggestion that theIL2RAlocus is associated with SLE and showed some evidence of association with AAV. Soluble IL-2RA concentrations correlate with rs11594656 genotype in quiescent disease in both AAV and SLE. Differential association of autoimmune diseases and SNPs within theIL2RAlocus suggests that theIL2RApathway may prove to play differing, as yet undefined, roles in each disease.
The forming limb skeleton serves as a signaling center for limb vasculature patterning via regulation ofVegf
Authors: Eshkar-Oren Idit , Viukov Sergey V. , Salameh Sharbel , Krief Sharon , Oh Chun-do , Akiyama Haruhiko , Gerber Hans-Peter , Ferrara Napoleone , Zelzer Elazar
Published: March 2009

Limb development constitutes a central model for the study of tissue and organ patterning; yet, the mechanisms that regulate the patterning of limb vasculature have been left understudied. Vascular patterning in the forming limb is tightly regulated in order to ensure sufficient gas exchange and nutrient supply to the developing organ. Once skeletogenesis is initiated,limb vasculature undergoes two seemingly opposing processes: vessel regression from regions that undergo mesenchymal condensation; and vessel morphogenesis. During the latter, vessels that surround the condensations undergo an extensive rearrangement, forming a stereotypical enriched network that is segregated from the skeleton. In this study, we provide evidence for the centrality of the condensing mesenchyme of the forming skeleton in regulating limb vascular patterning. Both Vegf loss- and gain-of-function experiments in limb bud mesenchyme firmly established VEGF as the signal by which the condensing mesenchyme regulates the vasculature. Normal vasculature observed in limbs where VEGF receptors Flt1, Flk1, Nrp1 and Nrp2 were blocked in limb bud mesenchyme suggested that VEGF, which is secreted by the condensing mesenchyme, regulates limb vasculature via a direct long-range mechanism. Finally, we provide evidence for the involvement of SOX9 in the regulation of Vegf expression in the condensing mesenchyme. This study establishes Vegf expression in the condensing mesenchyme as the mechanism by which the skeleton patterns limb vasculature.
Stress distribution of a coated film with an interlayer under elastohydrodynamic lubrication conditions
Authors: Fujino T , Iwamoto K , Akuzawa N , Tanaka K
Published: March 2009

In recent years, there have been advances in techniques for improving sliding performance by using coated films possessing superior tribological properties to reduce failure of mechanical elements. Those techniques are often used under severe conditions, such as elastohydrodynamic lubrication (EHL). In this paper, to devise the optimum design of a coated film with an interlayer, the stresses generated in such a coated film are analysed by using a three-dimensional numerical analysis method, and the strength of the film is evaluated numerically. As a result, it is shown that, when the ratio of the modulus of elasticity of the coated film, Ec, to that of the substrate, Es, is 0.50, it is preferable that the thicknesses of the coated film and the interlayer be larger, and that the modulus of elasticity of the interlayer range from that of the coated film to that of the substrate. Furthermore, it is shown that in the case of Ec/ Es=2.00, it is preferable to have a thicker interlayer irrespective of the values of the moduli of elasticity of the coated film and the interlayer.
Roles of adsorbed film and gel layer in hydration lubrication for articular cartilage
Authors: Murakami T , Nakashima K , Sawae Y , Sakai N , Hosoda N
Published: March 2009

To maintain low friction and low wear in natural synovial joints, adsorbed film formation on articular cartilage surface appears to play an important role in mixed or boundary lubrication regime where local direct contact occurs. Furthermore, the proteoglycan gel layer at the uppermost superficial zone in articular cartilage appears to play an important role in preserving low friction and low wear by the hydration lubrication mechanism even after removal of adsorbed film. However, the interaction or synergistic action between adsorbed film and hydrated film/surface has not yet been clarified. To examine the roles of adsorbed film and gel layer on articular cartilage surface in hydration lubrication, the changes in friction were observed in the reciprocating test of articular cartilage against a glass plate, at repeated rubbing including restarting after interrupting—unloading process. It is noticed that at restarting immediately after loading, hydration lubrication is expected to become effective. The lubricating roles of protein-adsorbed film in hydration lubrication are discussed on the basis of experimental results in both cases with and without surface gel layer. The comparison of albumin and γ -globulin is described in connection with the existence of a gel layer.
E. coli RNase III(E38A) generates discrete-sized products from long dsRNA
Authors: Xiao Jianping , Feehery Caitlin E. , Tzertzinis George , Maina Claude V.
Published: March 2009

Ribonuclease III (RNase III) represents a highly conserved family of double-strand-specific endoribonucleases that are important for RNA processing and post-transcriptional gene regulation in both prokaryotes and eukaryotes. We constructed a single amino acid substitution (E38A) of RNase III that shows a unique and useful enzymatic activity. It produces a dsRNA product of a discrete size migrating as 23 base pairs (bp) when given a long dsRNA as a substrate in an easy-to-control reaction. We demonstrate that the RNase III(E38A) mutant produces the 23-bp dsRNA product by making a double-strand cleavage of the long dsRNA substrate with the product being protected from further digestion. Using the hairpin RNA R1.1 as a substrate, RNase III(E38A) cleaves at the primary site and remains bound to the RNA, thereby preventing cleavage at the secondary site. The 23-bp dsRNA product is demonstrated to be a pool of dsRNAs representative of the long dsRNA substrate and has RNA interference activity in mammalian tissue culture transfection experiments. The RNA interference activity suggests that the 23-bp dsRNA product has typical 2-nucleotide 3′ overhangs and behaves as siRNA thereby making it a useful tool in RNA interference experiments.
Protein-specific glycosylation: signal patches and cis-controlling peptidic elements
Authors: Hanisch Franz-Georg , Breloy Isabelle
Published: March 2009

The term ‘protein-specific glycosylation’ refers to important functional implications of a subset of glycosylation types that are under direct control of recognition determinants on the protein. Examples of the latter are found in the formation of the mannose-6-phosphate receptor ligand on lysosomal hydrolases, and in polysialylation of NCAM, which are regulated via conformational signal patches on the protein. Distinct from these examples, the β4-GalNAc modification of N-linked glycans on a selected panel of proteins, such as carbonic anhydrase or glycodelin, was demonstrated recently to require specific protein (sequence) determinants proximal to the glycosylation site that function as cis-regulatory elements. Another example of such a cis-regulatory element was described for the control of mammalian O-mannosylation. In this case, the structural features of substrate sites within the mucin domain of α-dystroglycan are necessary, but not sufficient for determining the transfer of mannose to Ser/Thr. Evidence has been provided that an upstream-located peptide is also essential. Such cis-controlling elements provide a higher level of protein specificity, because a putative glycosylation site cannot result from a single point mutation. Here, we highlight recent work on protein-specific glycosylation with particular emphasis on the above-cited examples and we will try to link protein-specific glycosylation to function.
A Framework for Field and Laboratory Studies for Ecological Risk Assessments in Wetland and Terrestrial Habitats: Two Case Studies
Authors: Linder G , Bollman M , Gillett C , King R , Nwosu J , Ott S , Wilborn D , Henderson G , fleeger TP , Darrow T , Lightfoot D
Published: March 2009

Field surveys are frequently required during an ecological risk assessment for a hazardous waste site. Depending upon habitat type, field and laboratory methods that were developed for hazard evaluation lend themselves directly to the ecological risk assessment process. For example, wetlands are frequently impacted by various anthropogenic chemicals, and field and laboratory methods have been developed to help focus laboratory testing routinely planned in site evaluation. Here we compare and contrast the field and laboratory methods used in evaluating wetlands that occurred in markedly different geographic settings and were impacted by two different, but relatively simple contaminant sources. Both field studies were completed as part of the baseline ecological risk assessment process, one being located at Milltown Reservoir wetlands in western Montana and the other in the high desert of south central Oregon. In conjunction with chemical analyses of soil, sediment, and water samples, biological and ecological evaluations yielded an integrated evaluation of ecological effects and exposure at each site, which is critical information for any baseline ecological assessment. Overall, the field activities at each site illustrate the role that laboratory and field screening methods play in ecological management of waste sites.
Non-Linear Oscillations Detected by Multivariate Analysis in Microcosm Toxicity Tests: Implications for Risk Assessment and Biomonitoring.
Authors: Landis WG , Matthews RA , Markiewicz AJ , Matthews GB
Published: March 2009

This study compares the dynamics of the effects of the water soluble fraction (WSF) of both Jet-A and JP-4 using the Standard Aquatic Microcosm (SAM) using several types of multivariate analysis. In these studies we investigate the common assumption in environmental toxicology, that after the initial stress, ecosystems recover to resemble the control or reference state. This assumption may be based more on our inability to observe an ecosystem with sufficient resolution to detect differences, than reality. Among the more interesting effects observed in both studies were the shifts in time of population peaks and some other variables compared to non-dosed microcosms. In both experiments, multivariate analysis was able to differentiate oscillations that separate the treatments from the reference group, followed by what would normally appear as recovery, followed by another separation into treatment groups as distinct from the reference treatment. These patterns generally were not detected by conventional analysis.

Two sets of related explanations exist for the observed phenomenon. First, the addition of the toxicant initiates an alteration in the community so that the quality of the food resources for the later successional stages is significantly different from the control. This difference in resource quality and quantity leads to the repeated and replicated oscillations. The second explanation is that the oscillations are the result of the intrinsic complex and perhaps even chaotic behavior of population interactions. The initial impact of the toxicant re-set the dosed communities into different regions of the n-dimensional space where recovery may be an illusion due to the incidental overlap of the trajectories of the systems occurring along a few axes. Some of the implications of complex or chaotic dynamics upon the prediction of ecological risk and in biomonitoring are discussed.
A 28 Day Sediment Bioassay with the Marine Polychaete, NEREIS (NEANTHES) ARENACEODENTATA
Authors: Dillon TM , Moore DW , Reish DJ
Published: March 2009

A protocol for conducting a 28 day sediment bioassay with the marine polychaete, Nereis (Neanthes) arenaceodentata is described. Primary application is the regulatory evaluation of dredged material. Test endpoints are survival and estimated individual growth rate. Bioassays are initiated by adding juvenile worms to 1L glass beakers (5 worms/beaker) containing aerated seawater (30 ‰) and 2–3 cm of sediment. Temperature is 20°C and photoperiod 12h. Worms are fed twice weekly, seawater renewed weekly and water quality monitored throughout. After 28 days, the number of survivors per beaker is recorded. Worms in each replicate are dried as a pool. Estimated individual dry weight is calculated by dividing number of survivors into the pooled dry weight biomass. Growth rate (mg dry weight day-1) is calculated by subtracting initial from final dry weights and dividing by the exposure period (28 d). Performance criteria for positive and negative controls are discussed as well as guidance for interpreting bioassay results. Although designed for the regulatory evaluation of dredged material, this chronic sublethal bioassay can be applied to other assessments of sediment quality.
Using Grass Shrimp Embryos to Determine the Effects of Sediment on the Toxicity and Persistence of Diflubenzuron in Laboratory Microcosms
Authors: Wilson JEH , Cunningham PA , Evans DW , Costlow JD
Published: March 2009

Grass shrimp (Palaemonetes pugio) embryos were used to determine the effects of estuarine sediment on the toxicity and persistence of diflubenzuron (DFB) in two laboratory microcosm systems. The experimental microcosms contained DFB in seawater with sediment and DFB in seawater without sediment while the control microcosms contained seawater with sediment and seawater without sediment. Concentrations of DFB in seawater were determined by high performance liquid chromatography (HPLC) analysis of water samples collected from the DFB-treated microcosms. The estimated half-life of DFB in seawater was 18.7d in the microcosm without sediment compared to 5.2d in the system with sediment. The toxicity of aged DFB from the microcosms (initial nominal concentration = 10 μg/L) was determined by exposing 5-day old embryos of Palaemonetes pugio to 1 L of seawater (withdrawn from the microcosms) for 4d in a static system. Delayed toxicity was monitored at the larval stage. Toxicity end-points studied were: hatchability of the eggs, morphological abnormality of the larvae and larval viability. The results indicate that the presence of organic sediment in the DFB-treated microcosm significantly reduced the efficacy of DFB in seawater. The initial 10 μg/L DFB in the DFB-sediment microcosm aged for 30d before delayed toxicity was reduced to a non-significant level. By day 30, embryos reared in seawater from DFB-sediment microcosm produced larvae with no significant morphological abnormality and larval viability was comparable to the controls. Embryos reared in seawater from DFB-seawater microcosm (devoid of sediment) produced larvae with severe abnormalities and very low viability even after the solution aged for 65d. Hatchability of the eggs was not significantly affected by seawater from either of the DFB-treated microcosms.
A Comparative Analysis of the Toxicity of Boron Compounds to Freshwater and Saltwater Species
Authors: Hovatter PS , Ross RH
Published: March 2009

Inorganic borates and boric acid (boron-oxygen compounds) enter the environment as contaminants from the manufacture and industrial and household use of boron-containing compounds; from borax mining; and from coal, oil, and geothermal power generation. In general, boron compounds are more toxic to freshwater invertebrates than to freshwater fishes, with 48-hr LC50 values ranging from <52–226 mg B/L in the water flea (Daphnia magna) and 96-hr LC50 values ranging from 332–979 mg B/L in fathead minnows (Pimephales promelas) and mosquitofish (Gambusia affinis). Data also indicate that boron compounds are more toxic to saltwater crustaceans and fish than to freshwater species, with a 24-hr LC50 of 28.35 mg B/L in the saltwater isopod (Limnoria lignorum) and a 96-hr LC50 of 74 mg B/L in dab (Limanda limanda). A comparison of the acute toxicity of boron-oxygen compounds to adult and early developmental stages of fishes and invertebrates indicates that most species are more sensitive to sodium borates (sodium perborate > borax) than to boric acid. This increased toxicity may be attributed to a pH shift into the alkaline range, which in fish results in increased mucus formation and crippling behavior.
Net Photosynthesis and Respiration of Sago Pondweed (Potamogeton Pectinatus) Exposed to Herbicides
Authors: Fleming WJ , Ailstock MS , Momot JJ
Published: March 2009

We determined net photosynthesis and respiration rates for sago pondweed (Potamogeton pectinatus) exposed to various concentrations of 11 herbicides widely used in Maryland during the past decade. Net photosynthesis and respiration were determined by measuring changes in the oxygen content of solutions containing dilutions of technical grade herbicides. At 20–22° C and 58 μmol/m2/sec of photosynthetically active radiation (PAR), oxygen production of undosed plants averaged 0.72–2.03 mg/g fresh wt/h. Respiration rates of undosed plants averaged 0.46–0.60 mg O2/g fresh wt/h. Nominal herbicide concentrations (ng/L) that reduced net photosynthesis by 50 percent (IC50) were: metribuzin, 8; atrazine, 29; cyanazine, 32; linuron, 70; simazine, 164; and paraquat, 240. IC50 values for 2,4-D, acifluorfen, glyphosate and metolachlor exceeded the maximum test concentration of 10,000 ng/L. The IC50 value for alachlor was estimated to be between 1,000 and 10,000 ng/L. None of the herbicides tested had a significant effect on dark respiration.
Recent Developments in LCA and Critical Issues
Authors: Postlethwaite D
Published: March 2009

Lifecycle Assessment (LCA) is a fast growing technique which is now being widely applied. The methodology for conducting LCA's is being developed and refined and attempts are underway to set up agreed working procedures and standards. Foremost amongst these are the activities of ISO, in developing formal standards, and SETAC, in resolving methodological issues, such as energy accounting and co-product allocation, and, especially, in deriving an agreed Code of Practice. SETAC has also established, by means of consensus workshops, key bases for further necessary work on impact assessment (the relation of chemical emissions to actual environmental impacts) and data quality. Data availability is still a major factor limiting more widespread application of LCA, although some progress is being achieved, notably on raw material data for plastics and surfactants.
A Modified ASTM Semi-Continuous Activated Sludge Test to Compare Nonionic Surfactant Biological Removal
Authors: Nielsen AM , Filler PA , Heinze JE , Lachocki TM
Published: March 2009

The Semi-Continuous Activated Sludge (SCAS) test of the ASTM “Standard Test Method for Biodegradability of Alkylbenzene Sulfonates” (D2667-89) was modified and used to compare the biological removal of new carbohydrate-based surfactants (CBS). The SCAS test was modified in three ways: the units were miniaturized, natural sewage replaced synthetic sewage, and analysis for dissolved organic carbon (DOC) replaced methylene blue active substance as the analytical method. The modified test distinguished between compounds that underwent minimal to complete biological removal by establishing a percent removal at a “steady state” (typically reached within two weeks). The method is inexpensive, easy, and efficiently compares biological removal of surfactants or other water-soluble compounds. This study shows that random substitution of hydroxyl hydrogens on glucose inhibits biological removal. In contrast specific regio-substitution at the 3-O or 1-O positions did not inhibit biological removal.
ASTM Committee E-35 on Pesticides - Twenty Years Old!
Authors: Hazen JL , Butler BJ , Canning SP
Published: March 2009

ASTM Committee E-35 was organized in 1973 in response to the need for a recognized forum for addressing pesticide and associated environmental issues. The founding membership represented, industry, EPA, USDA, USDI, trade association, and university interests. Twenty years later, the organization is vital and continuing to function as a major forum for pesticide — related issues. The Committee membership has 73 established and 11 new Standard Definitions, Test Methods, Practices, and Guides which cover a diverse range of pesticide-related subjects.