bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of 17α-ethinylestradiol and bisphenol a on vertebral development in the fathead minnow (Pimephales Promelas)
Authors: Warner Kara E. , Jenkins Jeffrey J.
Published: June 2007

Growth, reproductive ability, and metabolic functions may be impaired by disruption of early endocrine patterning. Natural and synthetic estrogens detected in surface waters have been linked to reproductive endocrine signaling disruption in several species. The present study characterizes the nonreproductive morphological endpoint of vertebral anomalies in fish exposed to environmental estrogens. Estrogen is a proliferation-inducing compound in osteoblasts, regulating cartilage and bone deposition during development in vertebrates. The hypothesis for the present work is that xenobiotics with estrogenic activity adversely impact vertebral bone formation. Fathead minnows (Pimephales promelas) were exposed to 0.1 to 100 μg/L 17α-ethinylestradiol (EE2) and 0.1 to 1,000 μg/L bisphenol A (BPA) from egg stage (24 h postfertilization) to 25 to 26 d posthatch. Fish were measured for length and analyzed microscopically to determine degree of skeletal development (developmental score) and the occurrence of spinal abnormalities, including vertebral compression, bone fusion, and spinal curvatures. Fish length and developmental score were inversely related to vertebral malformations in exposed fish. Skeletal developmental was affected significantly in EE2-exposed fish: Vertebral malformations were observed in up to 62% of fish in a nonmonotonic dose-response. However, BPA did not significantly impair skeletal development or induce vertebral malformations. The bioassay results suggest vertebral bone development is a potential endpoint of endocrine disruption from potent estrogenic compounds in surface waters.
Subacute toxicity of oral 2,6-dinitrotoluene and 1,3,5-trinitro-1,3,5-triazine (RDX) exposure to the northern bobwhite (Colinus virginianus)
Authors: Johnson Mark S. , Quinn Michael J. , Bazar Matthew A. , Gust Kurt A. , Escalon B. Lynn , Perkins Edward J.
Published: June 2007

Military activities associated with training have resulted in soil residues of munition compounds and their breakdown products. Often, these areas are valuable habitats used by birds. To evaluate the possibility of adverse effects in birds, the effects from oral exposures of 2,6-dinitrotoluene (2,6-DNT) and 1,3,5-trinitro-1,3,5-triazine (RDX) were tested using a controlled dosing regime in northern bobwhite (Colinus virginianus). Nine groups of birds of mixed sex received either corn oil or 50, 100, 190, or 350 mg 2,6-DNT/kg body weight/d or 20, 80, 125, or 180 mg RDX/kg body weight/d mixed in corn oil via gavage for 14 d. Etiology of disease was markedly different between compounds. Increased RDX exposure caused an inverse relationship to time of death, symptoms including clonic followed by tonic convulsions, and death shortly thereafter. Brain concentrations of RDX postmortem, however, were relatively consistent (mean ± standard error, 20.5 ± 2.9 mg/kg tissue). Observations of 2,6-DNT effects included gastrointestinal distress, dehydration, and a reduction in body mass and feed consumption. Together, these data suggest that RDX is more toxic from short, repeated exposures than 2,6-DNT, resulting in central nervous system—related effects, whereas 2,6-DNT causes gastrointestinal disturbances at higher exposures.
Summary of potable well monitoring conducted for aldicarb and its metabolites in the United States in 2005
Authors: Jones Russell L. , Allen Richard
Published: June 2007

United States potable well monitoring in the Pacific Northwest, California, Texas, Mississippi delta, and the Southeast was conducted in 2005 to provide estimates of dietary exposure to aldicarb carbamate residues (aldicarb and its two carbamate metabolites) in potentially vulnerable potable wells. Samples were analyzed from 1,673 drinking water wells in nine major use areas that were within 300 m of fields treated at least once with aldicarb between 2002 and 2005. Analyses were performed with a high-performance liquid chromatography/tandem mass spectrometry analytical method with limits of quantitation of 0.021 μg/L for aldicarb and aldicarb sulfone and 0.027 μg/L for aldicarb sulfoxide. The method detection limits were 0.0070 μg/L for aldicarb and aldicarb sulfone and 0.0090 μg/L for aldicarb sulfoxide. Samples from 1,513 of the 1,673 wells contained no aldicarb carbamate residues. Only 10 wells had total aldicarb carbamate residues above 1 μg/L, the maximum being 2.9 μg/L. All residues were below the U.S. Environmental Protection Agency Health Advisory Limit (HAL) of 10 μg/L. Given the number of samples collected in this study, there is a 95% confidence level that the maximum concentration in this study exceeds the 99.8th percentile of concentrations of all potable wells located within 300 m of fields recently treated with aldicarb. Therefore, the data from this study show that the restrictions and management practices on the current product label continue to be effective in preventing residues in excess of the 10 μg/L HAL in potable wells in these use areas.
Feeding inhibition in the soil collembolanFolsomia candidaas an endpoint for the estimation of organic waste ecotoxicity
Authors: Domene Xavier , Natal-da-Luz Tiago , Alcañiz Josep M. , Andrés Pilar , Sousa José Paulo
Published: June 2007

Despite the increasing quantities of organic wastes that are being reused in soils, there are few studies that focus on the selection of bioassays for the ecotoxicological risk assessment of organic wastes to soils. In the present study, differences in feeding inhibition in the soil collembolan Folsomia candida were evaluated as an ecotoxicological endpoint for the assessment of risk to soils amended with polluted organic wastes. Seven organic wastes (dewatered sewage sludges, thermally dried sewage sludges, composted sewage sludges, and a thermally dried pig slurry) were tested. These wastes had different origins, treatments, and pollutant burdens, and were selected as a representative sample of the wide variety of wastes currently generated. A clear dose response was observed for this parameter, with an increase in percentage of individual feeding inhibition with increased doses of organic wastes. More significantly, feeding inhibition correlated highly with mortality and reproduction inhibition in the different wastes. Composted sludges displayed the lowest toxicity, followed by thermally dried sludge and dewatered sludge. Thermally dried pig slurry showed the highest toxicity for feeding, with lower median effective concentration (EC50) values than the lowest dose tested. Among waste physicochemical parameters and pollutants, low organic matter stability appeared to be the main predictor of potential adverse effects on soil fauna, because it correlated significantly with feeding inhibition and mortality. Furthermore, feeding inhibition tests were run over a short exposure time (less than 7 d), which, together with the results obtained, makes this bioassay a good screening tool for organic waste toxicity.
Pathways to Smoking Cessation Among African American and Puerto Rican Young Adults
Authors: Marcus Stephen E. , Pahl Kerstin , Ning Yuming , Brook Judith S.
Published: June 2007

Objectives. We examined the pathways to smoking cessation between late adolescence and young adulthood.

Methods. We obtained data from a sample of urban African American and Puerto Rican young adults (N=242), mean age 19 years, who reported tobacco use and determined cessation rates between late adolescence and young adulthood. We used structural equation modeling to examine the pathways of positive family relations, family smoking, maladaptive personality attributes, and substance use to smoking cessation.

Results. A mediational pathway linked the absence of positive family relations with maladaptive personality attributes, both of which were related to substance use and ultimately smoking cessation. Substance use mediated the path between family smoking and smoking cessation.

Conclusions. The results suggest that a positive relationship with one’s parents, less smoking in the family, conventional personality attributes, and little or no other substance use facilitate smoking cessation among young adults.
The Influence of Subjective Social Status on Vulnerability to Postpartum Smoking Among Young Pregnant Women
Authors: Reitzel Lorraine R. , Vidrine Jennifer I. , Li Yisheng , Mullen Patricia D. , Velasquez Mary M. , Cinciripini Paul M. , Cofta-Woerpel Ludmila , Greisinger Anthony , Wetter David W.
Published: June 2007

Objectives. Associations between subjective social status, a subjective measure of socioeconomic status, and predictors of risk for postpartum smoking were examined among 123 pregnant women (aged 18–24 years) who stopped smoking because of pregnancy. The goal was to identify how subjective social status might influence the risk for postpartum smoking and to elucidate targets for intervention.

Methods. We used multiple regression equations to examine the predictive relations between subjective social status and tobacco dependence, self-rated likelihood of postpartum smoking, confidence, temptations, positive and negative affect, depression, stress, and social support. Adjusted analyses were also conducted with control for race/ethnicity, education, income, and whether participant had a partner or not (partner status).

Results. In unadjusted and adjusted analyses, subjective social status predicted tobacco dependence, likelihood of postpartum smoking, confidence, temptations, positive affect, negative affect, and social support. Adjusted analyses predicting depression and stress approached significance.

Conclusions. Among young pregnant women who quit smoking because of pregnancy, low subjective social status was associated with a constellation of characteristics indicative of increased vulnerability to postpartum smoking. Subjective social status provided unique information on risk for postpartum smoking over and above the effects of race/ethnicity, objective socioeconomic status, and partner status.
Prospective Predictors of Long-Term Abstinence Versus Relapse Among Smokers Who Quit as Young Adults
Authors: Macy Jonathan T. , Seo Dong-Chul , Chassin Laurie , Presson Clark C. , Sherman Steven J.
Published: June 2007

Objectives. We sought to identify prospective predictors of long-term abstinence versus relapse among individuals who quit smoking as young adults.

Methods. Participants from an ongoing longitudinal study of smoking who had quit for at least 1 year between the ages of 18 and 24 years (n=327) were divided into those who later reported not smoking for more than 5 years (long-term abstinence) or reported current smoking, defined as smoking at least monthly (relapse). Logistic regression was used to examine odds ratios (ORs) of prospective predictors of long-term abstinence versus relapse.

Results. Overall, 67% of participants maintained long-term abstinence and 33% relapsed. The strongest predictor of avoiding relapse was marrying a nonsmoker (adjusted OR [AOR]=0.07; 95% confidence interval [CI]=0.03, 0.21). Other predictors included making 1 lifetime quit attempt (AOR=0.13; 95% CI=0.04, 0.44), having as a young adult only 1 parent who smoked (AOR=0.23; 95% CI=0.06, 0.93), and working in a completely smoke-free building (AOR=0.13; 95% CI=0.03, 0.58).

Conclusions. The factors related to smoking in the social environment played the largest role in predicting long-term abstinence versus relapse.
The Incidence of “Causal” Statements in Teaching-and-Learning Research Journals
Authors: Robinson Daniel H. , Levin Joel R. , Thomas Greg D. , Pituch Keenan A. , Vaughn Sharon
Published: June 2007

The authors examined the methodologies of articles in teaching-and-learning research journals, published in 1994 and in 2004, and classified them as either intervention (based on researcher-manipulated variables) or nonintervention. Consistent with the findings of Hsieh et al., intervention research articles declined from 45% in 1994 to 33% in 2004. For nonintervention articles, the authors recorded the incidence of “causal” statements (e.g., if teachers/schools/parents did X, then student/child outcome Y would likely result). Nonintervention research articles containing causal statements increased from 34% in 1994 to 43% in 2004. It appears that at the same time intervention studies are becoming less prevalent in the teaching-and-learning research literature, researchers are more inclined to include causal statements in nonintervention studies.
Reading Rescue: An Effective Tutoring Intervention Model for Language-Minority Students Who Are Struggling Readers in First Grade
Authors: Ehri Linnea C. , Dreyer Lois G. , Flugman Bert , Gross Alan
Published: June 2007

The Reading Rescue tutoring intervention model was investigated with 64 low–socioeconomic status, language-minority first graders with reading difficulties. School staff provided tutoring in phonological awareness, systematic phonics, vocabulary, fluency, and reading comprehension. Tutored students made significantly greater gains reading words and comprehending text than controls, who received a small-group intervention (d = 0.70) or neither intervention (d = 0.74). The majority of tutored students reached average reading levels whereas the majority of controls did not. Paraprofessionals tutored students as effectively as reading specialists except in skills benefiting nonword decoding. Paraprofessionals required more sessions to achieve equivalent gains. Contrary to conventional wisdom, results suggest that students make greater gains when they read text at an independent level than at an instructional level.
Organizational Strategies for Promoting Instructional Change: Implementation Dynamics in Schools Working With Comprehensive School Reform Providers
Authors: Rowan Brian , Miller Robert J.
Published: June 2007

This article develops a conceptual framework for studying how three comprehensive school reform (CSR) programs organized schools for instructional change and how the distinctive strategies they pursued affected implementation outcomes. The conceptual model views the Accelerated Schools Project as using a system of cultural control to produce instructional change, the America's Choice program as using a model of professional control, and the Success for All program as using a model of procedural control. Predictable differences in patterns of organizing for instructional improvement emerged across schools working with these three programs, and these patterns were found to be systematically related to patterns of program implementation. In particular, the two CSR programs that were organized to produce instructional standardization produced higher levels of instructional change in the schools where they worked. The results of the study suggest organizational strategies program developers can use to obtain implementation fidelity in instructional change initiatives.
Effects of anti–glutamic acid decarboxylase antibodies associated with neurological diseases
Authors: Manto Mario‐Ubaldo , Laute Marie‐Aline , Aguera Michèle , Rogemond Véronique , Pandolfo Massimo , Honnorat Jérome
Published: June 2007

Objective

Glutamic acid decarboxylase (GAD) catalyzes the conversion of glutamic acid into GABA. GAD autoantibodies (GAD‐Ab) have been described in diabetes mellitus and in diseases involving the central nervous system such as stiff‐person syndrome and cerebellar ataxia. However, the pathogenic role of GAD‐Ab in neurological diseases remains a matter of debate.

Methods

Using neurophysiological and neurochemical methods, we analyzed the effects of intracerebellar and paraspinal administration of GAD‐Ab in rats.

Results

Intracerebellar administration of IgG from patients with GAD‐Ab and neurological involvement (IgG‐GAD) blocked the potentiation of the corticomotor response normally associated with trains of repetitive peripheral nerve stimulation. When injected in the lumbar paraspinal region, IgG‐GAD induced continuous motor activity with repetitive discharges, abnormal exteroceptive reflexes, and increased excitability of anterior horn neurons, as assessed by F/M ratios. Furthermore, IgG‐GAD significantly reduced the N‐methyl‐D‐aspartate–mediated production of nitric oxide in cerebellar nuclei and impaired the synaptic regulation of glutamate after N‐methyl‐D‐aspartate administration. These effects were not observed after administration of IgG from the following groups: (1) patients with GAD‐Ab, diabetes mellitus, and without neurological complications; and (2) control patients.

Interpretation

These results indicate that stiff‐person syndrome and cerebellar ataxia are the direct consequence of antibody‐mediated neuronal dysfunction. Ann Neurol 2007;61:544–551
Endogenous HLA–DR–restricted presentation of the cartilage antigens human cartilage gp‐39 and melanoma inhibitory activity in the inflamed rheumatoid joint
Authors: van Lierop M. J. C. , den Hoed L. , Houbiers J. , Vencovsky J. , Ruzickova S. , Krystufkova O. , van Schaardenburg M. , van den Hoogen F. , Vandooren B. , Baeten D. , de Keyser F. , Sønderstrup G. , Bos E. , Boots A. M.
Published: June 2007

Objective

The cartilage proteins melanoma inhibitory activity (MIA) and human cartilage gp‐39 (HC gp‐39) are candidate autoantigens in rheumatoid arthritis (RA). The present study was undertaken to investigate the endogenous HLA–DR4–restricted presentation of these self proteins, in order to seek in vivo evidence in support of their potential immunologic role.

Methods

MIA and HC gp‐39 were assessed in synovial fluid (SF) by enzyme‐linked immunosorbent assay and in synovial tissue (ST) by immunohistochemistry. Presentation by SF cells was investigated using specific, HLA–DR–restricted T cell hybridomas.

Results

MIA and HC gp‐39 were detected in RA SF and ST, as well as in specimens from patients with other forms of arthritis. When HC gp‐39–specific and MIA‐specific HLA–DR4–restricted T cell hybridomas raised in HLA–DR4–transgenic mice were incubated with RA SF cells as antigen‐presenting cells in the presence of HC gp‐39 or MIA peptides, the corresponding T cell hybridomas showed strong responses, which were blocked by anti–HLA–DR antibodies. Weaker but qualitatively similar responses were observed with exogenous protein, indicating uptake and processing of these antigens by SF cells. More importantly, without addition of peptide or protein, endogenous presentation of MIA and HC gp‐39 was detected in SF cells from 53% and 80% of HLA–DRB1*0401–positive RA patients, respectively. In addition, SF cells from 3 of 10 patients with spondylarthritis exhibited endogenous HC gp‐39 presentation.

Conclusion

These data indicate that immunodominant epitopes of MIA and HC gp‐39 are actively presented in an HLA–DR–restricted manner in the inflamed RA joint. The question remains as to whether this leads to activation of autoreactive T cells, which could play a role in either the immunopathology or the immunomodulation of arthritis.
Autoimmune diseases in a Danish cohort of 4,866 carriers of constitutional structural chromosomal rearrangements
Authors: Bache Iben , Nielsen Nete M. , Rostgaard Klaus , Tommerup Niels , Frisch Morten
Published: June 2007

Objective

Constitutional structural chromosomal rearrangements (CSCRs) have facilitated the identification of genes associated with early‐onset monogenic disorders and, more recently, genes associated with common and late‐onset disorders. In an attempt to find genetic clues to their etiologies, we studied the risk of autoimmune diseases in a Danish cohort of CSCR carriers.

Methods

We followed up 4,866 CSCR carriers over 71,230 person‐years (1980 through 2004) for autoimmune diseases recorded in the Danish Hospital Discharge Register. Standardized incidence ratios (SIRs) and 95% confidence intervals (95% CIs) served as measures of the relative risk. To identify possible candidate loci for autoimmune diseases, the reported chromosomal breakpoints and deletions in CSCR carriers who developed autoimmune diseases were compared with previously suggested loci for these diseases.

Results

The overall risk of any autoimmune disease among CSCR carriers was inconspicuous (SIR 1.2 [95% CI 0.95–1.5]; n = 74 cases observed versus 61.3 expected), but carriers of rearrangements involving chromosomes 2, 19, and 21 were at significantly increased risk. For the specific autoimmune diseases studied, cohort members were at significantly increased risk of Dupuytren's contracture, pernicious anemia, and juvenile rheumatoid arthritis (JRA). Sixteen carriers who developed an autoimmune disease had a chromosomal breakpoint or deletion coinciding with a previously suggested locus, including deletions 18p11, 18q22, and 22q11 associated with JRA.

Conclusion

CSCR carriers do not have a generalized predisposition to autoimmune diseases. However, we confirmed a number of reported susceptibility loci for JRA, and we suggest new susceptibility loci on chromosomes 5 and 11 for Dupuytren's contracture, and 19p13 as a possible shared susceptibility locus for a range of autoimmune diseases.
Aspirin for primary thrombosis prevention in the antiphospholipid syndrome: A randomized, double‐blind, placebo‐controlled trial in asymptomatic antiphospholipid antibody–positive individuals
Authors: Erkan Doruk , Harrison Melanie J. , Levy Roger , Peterson Margaret , Petri Michelle , Sammaritano Lisa , Unalp‐Arida Aynur , Vilela Veronica , Yazici Yusuf , Lockshin Michael D.
Published: June 2007

Objective

To determine the efficacy of a daily dose of 81 mg aspirin in primary thrombosis prevention in asymptomatic, persistently antiphospholipid antibody (aPL)–positive individuals (those with positive aPL but no vascular and/or pregnancy events).

Methods

The Antiphospholipid Antibody Acetylsalicylic Acid (APLASA) study was a multicenter, randomized, double‐blind, placebo‐controlled clinical trial in which asymptomatic, persistently aPL‐positive individuals were randomized to receive a daily dose of 81 mg of aspirin or placebo. In a separate observational and parallel study, asymptomatic, persistently aPL‐positive individuals who were taking aspirin or declined randomization were followed up prospectively.

Results

In the APLASA study, 98 individuals were randomized to receive aspirin or placebo (mean ± SD followup period 2.30 ± 0.95 years), of whom 48 received aspirin and 50 received placebo. In the observational study, 74 nonrandomized individuals were followed up prospectively (mean ± SD followup period 2.46 ± 0.76 years); 61 received aspirin and 13 did not. In the APLASA study, the acute thrombosis incidence rates were 2.75 per 100 patient‐years for aspirin‐treated subjects and 0 per 100 patient‐years for the placebo‐treated subjects (hazard ratio 1.04, 95% confidence interval 0.69–1.56) (P = 0.83). Similarly, in the observational study, the acute thrombosis incidence rates were 2.70 per 100 patient‐years for aspirin‐treated subjects and 0 per 100 patient‐years for those not treated with aspirin. All but 1 patient with thrombosis in either study had concomitant thrombosis risk factors and/or systemic autoimmune disease at the time of thrombosis.

Conclusion

Our results suggest that asymptomatic, persistently aPL‐positive individuals do not benefit from low‐dose aspirin for primary thrombosis prophylaxis, have a low overall annual incidence rate of acute thrombosis, and develop vascular events when additional thrombosis risk factors are present.
Hsp90 mediates insulin‐like growth factor 1 and interleukin‐1β signaling in an age‐dependent manner in equine articular chondrocytes
Authors: Boehm Amber K. , Seth Mayank , Mayr Karen G. , Fortier Lisa A.
Published: June 2007

Objective

Many metabolic processes in chondrocytes thought to contribute to age‐related changes in the extracellular matrix are influenced by known roles of Hsp90. Age‐related decreases in the level of Hsp90 have been documented in numerous cell types and could contribute to cartilage degeneration. The aim of this study was to investigate the roles of age and Hsp90 in insulin‐like growth factor 1 (IGF‐1) and interleukin‐1β (IL‐1β) signaling in chondrocytes.

Methods

Levels of Hsp90 messenger RNA (mRNA) and protein, with respect to age, were determined by quantitative real‐time polymerase chain reaction (PCR) and Western blot analysis, respectively. The Hsp90 inhibitor geldanamycin (50 nM, 100 nM, or 500 nM) was used to assess age‐related responses to Hsp90 with concurrent IGF‐1 or IL‐1β stimulation of chondrocytes. Quantitative real‐time PCR was used to measureCOL2A1and matrix metalloproteinase 13 (MMP13) gene expression; Western blot analysis was performed to determine the phosphorylation status of p42/44 and Akt/protein kinase B.

Results

The effects of Hsp90 inhibition with geldanamycin were concentration dependent. Inhibition of Hsp90 with 100 nMor 500 nMgeldanamycin blocked IGF‐1–induced cell proliferation, Akt and p42/44 activation, andCOL2A1expression. Basal and IL‐1β–induced up‐regulation ofMMP13mRNA was blocked by all concentrations of geldanamycin tested. Gain‐of‐function assays with Hsp90 resulted in increased expression ofMMP13mRNA.

Conclusion

These results suggest that Hsp90 is involved in opposing signaling pathways of cartilage homeostasis, and that catabolic responses are more sensitive to Hsp90 inhibition than are anabolic responses. Further studies are needed to determine the role of Hsp90 inhibition in osteoarthritis in order to assess its potential as a therapeutic target.
C1D is a major autoantibody target in patients with the polymyositis–scleroderma overlap syndrome
Authors: Schilders Geurt , Egberts Wilma Vree , Raijmakers Reinout , Pruijn Ger J. M.
Published: June 2007

Objective

To assess whether the recently discovered exosome‐associated proteins MPP6, C1D, KIAA0052/hMtr4, hSki2, and hSki8 are targeted by autoantibodies, and to determine whether these autoantibodies are accompanied by antibodies directed to the established exosome‐associated autoantigens PM–Scl‐75 and PM–Scl‐100.

Methods

Complementary DNAs encoding the recently identified human exosome–associated proteins were expressed as His‐tagged fusion proteins in Escherichia coli cells. Sera obtained from patients with several different autoimmune diseases were analyzed for the presence of autoantibodies directed to these proteins, in an enzyme‐linked immunosorbent assay (ELISA). The ELISA data obtained for C1D were confirmed by Western blot analysis, using recombinant C1D.

Results

All exosome‐associated proteins were found to be targeted by autoantibodies, although the frequency with which such antibodies occurred in patient sera was relatively low, with the exception of anti‐C1D antibodies. Autoantibodies recognizing C1D were detected in 7 of 30 patients (23%) with the polymyositis (PM)–scleroderma overlap syndrome; this frequency was similar to the frequencies for the established autoantigens PM–Scl‐75c (27%) and PM–Scl‐100 (23%). Importantly, several patients with the PM–scleroderma overlap syndrome had anti‐C1D antibodies but no anti–PM‐Scl antibodies. Anti‐C1D autoantibodies were observed in only 2 of 204 patients with other diseases, including PM, dermatomyositis, and scleroderma.

Conclusion

Our results demonstrate that the recently identified exosome‐associated protein C1D is a major autoantigen in patients with the PM–scleroderma overlap syndrome and suggest that the use of recombinant C1D as an autoantibody target may aid in diagnosis of the PM–scleroderma overlap syndrome.
Calcium signaling leads to mitochondrial depolarization in impact‐induced chondrocyte death in equine articular cartilage explants
Authors: Huser C. A. M. , Davies M. E.
Published: June 2007

Objective

Chondrocyte apoptosis is an important factor in the progression of osteoarthritis. This study aimed to elucidate the mechanisms involved upstream of caspase 9 activation and, in particular, calcium signaling and mitochondrial depolarization.

Methods

Articular cartilage explants obtained from healthy horses were subjected to a single impact load (500‐gm weight dropped from a height of 50 mm) and cultured in vitro for up to 48 hours. Chondrocyte death was quantified by the TUNEL method. Release of proteoglycans was determined by the dimethylmethylene blue assay. Weight change was measured, and mitochondrial depolarization was determined using JC‐1 staining. To assess the role of calcium signaling in impact‐induced chondrocyte death, explants were preincubated in culture medium containing various concentrations of calcium. Inhibitors were used to assess the role of individual signaling components in impact‐induced chondrocyte death.

Results

Calcium quenching, inhibitors of calpains, calcium/calmodulin‐regulated kinase II (CaMKII), and mitochondrial depolarization reduced impact‐induced chondrocyte death after 48 hours in culture. Transient mitochondrial depolarization was observed 3–6 hours following a single impact load. Mitochondrial depolarization was prevented by calcium quenching, inhibitors of calpain, CaMKII, permeability transition pore formation, ryanodine receptor, and the mitochondrial uniport transporter. Cathepsin B did not appear to be involved in impact‐induced chondrocyte death. The calpain inhibitor prevented proteoglycan loss, but the percentage weight gain and proteoglycan loss were unaffected by all treatments used.

Conclusion

Following a single impact load, calcium is released from the endoplasmic reticulum via the ryanodine receptor and is taken up by the mitochondria via the uniport transporter, causing mitochondrial depolarization and caspase 9 activation. In addition, calpains and CaMKII play important roles in causing mitochondrial depolarization.
Two HLA–B27 alleles differently associated with spondylarthritis, B*2709 and B*2705, display similar intracellular trafficking and oligomer formation
Authors: Giquel Benoit , Carmouse Sophie , Denais Céline , Cherfa Aïcha , Chimenti Maria‐Sole , Fert Ingrid , Hacquard‐Bouder Cécile , Breban Maxime , André Claudine
Published: June 2007

Objective

To examine whether and to what extent the intracellular trafficking features of HLA–B*2705, which is associated with the development of spondylarthritis (SpA), differ from those of HLA–B*2709 and HLA–B*0702, which are not associated with SpA.

Methods

HeLa cells were transfected with complementary DNA encoding for HLA–B proteins fused to Renilla luciferase or yellow fluorescent protein. The subcellular distribution of properly folded and unfolded/misfolded HLA–B proteins was examined by flow cytometry and confocal microscopy of cells labeled with ME1 and HC‐10 antibodies, respectively. HLA–B/HLA–B interactions were monitored in endoplasmic reticulum (ER)– and plasma membrane–enriched subcellular fractions, by bioluminescence resonance energy transfer (BRET).

Results

All 3 HLA–B alleles displayed a similar distribution pattern (properly folded heavy chain at the cell surface, unfolded/misfolded proteins only in the cytoplasm). By means of BRET, we provided evidence that both HLA–B*2705 and HLA–B*2709 formed more oligomers in the ER and the plasma membrane than did HLA–B*0702. The propensity of HLA–B*2705 to form oligomers in the ER was partly attributable to residue Cys67 of the molecule. For all 3 alleles, increased expression of HLA–B proteins was associated with intracytoplasmic accumulation of unfolded/misfolded proteins and intracellular vesicles, probably corresponding to expanded ER–Golgi intermediate compartments, in which these proteins accumulated together with the stress sensor BiP.

Conclusion

Our results suggest that the difference in disease susceptibility conferred by HLA–B*2705 and HLA–B*2709 cannot be explained by their different propensity to form dimers or misfolded proteins, thus presumably implicating other, still unknown factors.
Calcineurin modulates the catabolic and anabolic activity of chondrocytes and participates in the progression of experimental osteoarthritis
Authors: Yoo Seung‐Ah , Park Bo‐Hyoung , Yoon Hyung‐Ju , Lee Joo‐Yup , Song Joo‐Hyoun , Kim Hyun Ah , Cho Chul‐Soo , Kim Wan‐Uk
Published: June 2007

Objective

To determine whether intracellular calcineurin (Cn), a calcium‐activated phosphatase, regulates the anabolic and catabolic activities of chondrocytes, and is a potential target in the treatment of osteoarthritis (OA).

Methods

CnA expression was examined in cartilage tissue samples and cultured chondrocytes from OA patients, using immunohistochemistry and Western blot analysis, respectively. Concentrations of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases 1 (TIMP‐1) in the culture supernatants were determined using enzyme‐linked immunosorbent assay. Levels of nitric oxide (NO) and type II collagen (CII) were measured using the Griess reaction and Western blot analysis, respectively. In addition, the pathologic role of Cn was examined in an in vivo model in which experimental OA was induced in mice by injecting type VII collagenase into the knee joints.

Results

CnA was highly expressed in the chondrocytes of lesional OA cartilage. Cyclosporin A (CSA), a Cn inhibitor, inhibited spontaneous and interleukin‐1β–stimulated production of NO, MMP‐1, and MMP‐3 in chondrocytes. However, CSA increased the levels of production of CII, TIMP‐1, and transforming growth factor β. Similar changes in MMP‐1, NO, and CII expression levels in chondrocytes were observed after the targeted inhibition of Cn by overexpression of calcineurin binding protein 1, a natural Cn antagonist. Moreover, in the mouse model, animals treated with CSA showed a significant decrease in both the extent and the severity of cartilage damage, which were assessed macroscopically and microscopically, compared with vehicle‐treated animals.

Conclusion

These results suggest that CnA is critically involved in the catabolic and anabolic activities of chondrocytes as well as in the progression of experimental OA. Targeted inhibition of CnA may be an effective treatment strategy for OA.
Pathogenic effects of antimyeloperoxidase antibodies in patients with microscopic polyangiitis
Authors: Guilpain Philippe , Servettaz Amélie , Goulvestre Claire , Barrieu Sandrine , Borderie Didier , Chéreau Christiane , Kavian Niloufar , Pagnoux Christian , Guillevin Loïc , Weill Bernard , Mouthon Luc , Batteux Frédéric
Published: June 2007

Objective

Microscopic polyangiitis (MPA) is a small‐vessel vasculitis associated with antimyeloperoxidase (MPO) antibodies in 70% of patients. Anti‐MPO antibodies can trigger the release of MPO by neutrophils and monocytes, but their involvement in the pathogenesis of MPA is still questioned. The aim of this study was to investigate whether anti‐MPO antibodies can activate MPO to generate an oxidative stress that is potentially deleterious to the endothelium.

Methods

MPA sera, purified IgG from MPA sera, normal control sera, and purified IgG from normal sera were incubated with MPO coated onto microtitration plates. The peroxidase activity of MPO was evaluated by adding o‐phenylenediamine. Production of hypochlorous acid (HOCl) was determined by chemiluminescence. The cytotoxic properties of byproducts of MPO activation were tested on endothelial cells in culture.

Results

MPA sera with anti‐MPO antibodies were found to activate MPO in vitro (P < 0.0001 versus normal sera) and to generate HOCl (P < 0.001), as did IgG purified from MPA sera (P < 0.05). MPA sera without anti‐MPO antibodies and MPA IgG absorbed on MPO did not show these activities. The byproducts of MPO activation by MPA sera exerted a strong cytolytic activity on endothelial cells in culture (P < 0.01). Both HOCl production and endothelial lysis were abrogated by N‐acetylcysteine (NAC), an antioxidant molecule (P < 0.05 and P < 0.0001, respectively).

Conclusion

Anti‐MPO antibodies could play a pathogenic role in vivo by triggering an oxidative burst, leading to severe endothelial damage. Treatment of MPA patients with NAC might be proposed in an attempt to abrogate these deleterious phenomena.
User preference in published indexes
Authors: Gould Angela M.
Published: June 2007

A study of the importance to the user of various characteristics in the printed subject indexes to abstract journals and published literature, and the users' preference for the different formats available, was carried out. The investigation was made by means of a questionnaire which was answered by both library staff and scientists. The respondents compared particular index characteristics in a number of differing indexes and also commented on specific details of the indexes to Science Abstracts. The results highlighted the important characteristics and preferences, and differences in the pattern of use of printed subject indexes by the library staff and scientists where indicated. Recent changes in the indexes to Science Abstracts take account of the users' preferences.
Making on‐line search available in an industrial research environment
Authors: Lawrence Barbara , Weil Ben H. , Graham Margaret H.
Published: June 2007

On‐line interactive searching of several information bases through several service operators was introduced in an industrial research environment. Thorough knowledge of the information base and its structure in the search system is a major factor for successful searching, and differences among search systems do not present serious barriers. This new technique was most effectively used when the information specialist and the scientist searched as a team. On‐line searching is now an established search tool at Exxon Research and Engineering Company.
A framework for the study of emerging network technology
Authors: Penniman W. David , Krohn Richard E. , Kovacs Gabor J.
Published: June 2007

Emerging networks are classified in a variety of ways in current literature. The proposed framework distinguishes between computer, communication, and information networks and indicates how these three network types can be used to augment each other.
Reduction of data generation costs
Authors: Wilde Daniel U. , David Chafe H.
Published: June 2007

The difficulty and expense of acquiring textual material in machine‐readable form is a major barrier to more extensive use of computers in libraries. This paper discusses the reduction of data generation costs, by the use of the IBM MT/ST typewriter and tape converter to eliminate redundancy in keying opera‐ tions. Their use in the production of World Aluminum Abstracts is presented as a typical application.
RELEVANCE: A review of and a framework for the thinking on the notion in information science
Authors: Saracevic Tefko
Published: June 2007

Information science emerged as the third subject, along with logic and philosophy, to deal with relevance‐an elusive, human notion. The concern with relevance, as a key notion in information science, is traced to the problems of scientific communication. Relevance is considered as a measure of the effectiveness of a contact between a source and a destination in a communication process. The different views of relevance that emerged are interpreted and related within a framework of communication of knowledge. Different views arose because relevance was considered at a number of different points in the process of knowledge communication. It is suggested that there exists an interlocking, interplaying cycle of various systems of relevances.
Complementarity between a use study and a citation study in considering publication practices in the physical and social sciences
Authors: Rafsnider Jean
Published: June 2007

Comparisons of hard and soft science in user (Garvey) and citation (Price) studies were shown to exhibit a previously unnoticed complementarity. In particular, the lower utilization of recent citations by social scientists may be shown to reflect the greater time required for scientific work and subsequent publication of a social science research contribution as opposed to one from the physical sciences. This analysis offers an alternative to the view of hard and soft science offered by Price and raises several research questions regarding the relation between use and citation of scientific literatures.
A library network model
Authors: Rouse William B.
Published: June 2007

The performance of an interlibrary loan network is characterized by the probability of satisfying a request, delay in satisfying a request, total and unit costs, and processing load on each network member. In this article, a distributed queueing network is used to model this situation. The general structure can be specialized to a ring structure or a centralized structure. A hypothetical network situation is used to discuss the effects of network dispersion and distribution of resources on several policy issues. These issues include request routing, reimbursement and possible investments in computer technology.
Relevance weighting of search terms
Authors: Robertson S. E. , Jones K. Sparck
Published: June 2007

This paper examines statistical techniques for exploiting relevance information to weight search terms. These techniques are presented as a natural extension of weighting methods using information about the distribution of index terms in documents in general. A series of relevance weighting functions is derived and is justified by theoretical considerations. In particular, it is shown that specific weighted search methods are implied by a general probabilistic theory of retrieval. Different applications of relevance weighting are illustrated by experimental results for test collections.
Automatic aids to profile construction
Authors: Robson Alan , Longman Janet S.
Published: June 2007

A function (term specificity) may be defined such that it gives a measure of the potential usefulness of a search term, when it is incorporated in a profile.

A system is described for the production of specificity lists, using an iterative procedure involving textual analysis of the data base combined with an analysis of the relevance of references selected by this procedure. Such lists are produced for single terms, term pairs and term fragments.

The lists are combined by program to give search profiles. The results of searching these profiles are compared with those from corresponding profiles produced by conventional means and it is shown that, in general, the automatic profiles are cheaper to construct and search, and yet perform similarly to the conventional profiles.
On the naranan interpretation of Bradford's law
Authors: Hubert John J.
Published: June 2007

The Naranan interpretation of the original form of Bradford's Law does not follow from a stochastic argument based on his assumptions.
Variety generation—A reinterpretation of Shannon's mathematical theory of communication, and its implications for information science
Authors: Lynch Michael F.
Published: June 2007

The conventional interpretation of Shannon's mathematical theory of communication in relation to textual material is unduly restrictive and unhelpful. A reinterpretation which is based on the definition of new symbol sets, comprising approximately equally‐frequent strings of characters, is presented. It is shown to have wide applicability in computer‐processing of texts. Moreover, it provides a more general formalism for considering methods of representing, storing and retrieving the subject content of documents.
The diffusion of core publications in american sociology
Authors: Oromaner Mark
Published: June 2007

Citations to articles published during 1960 in three “core” sociological journals, cited in ten sociological journals (1961‐70), are examined. One‐third of the articles were not cited at all, while only eleven percent of the cited articles were cited in more than one‐half (six or more) of the journals. Articles are more likely to be cited in core journals than in specialized journals. Studies of the reading and citing practices of authors are needed. Finally, it is suggested that the core journals may not play an integrating role within sociology and that greater attention should be focused on the specialty journals.
The identifier method of measuring use as applied to modeling the circulation use of books from a university library
Authors: Turner Stephen J.
Published: June 2007

Many authors have studied statistics on time since last use as possible useful aids for weeding collections. These approaches are special cases of a more general identifier method which allows greater flexibility in the selection and determination of objective retirement criteria. The general theory and a specific case study are presented in an effort to indicate both the flexibility and practicality of the method. The report concludes with a list of some of the more important considerations for execution of the general approach.
The application of function descriptors to the development of an information system topology
Authors: Swanson E. Burton
Published: June 2007

A type of descriptor, termed a Function Descriptor, is suggested for application to the description and classification of information systems, and for the development of an information system typology. In the exploratory description of 25 systems, a list of 83 Function Descriptors was developed. In a small experiment undertaken, it was seen that consensual agreement in the application of the Function Descriptors is not simply achieved. Several suggestions are made for dealing with the difficulties of application, including the classification of information system functions into three types: utilization‐level functions, production‐level functions, and operation‐level functions. The establishment of an Information System Reference Center is proposed as a basis for the continuance of the research.
A metatheory for the development of a science of information
Authors: Dow John T.
Published: June 2007

Information science would do well to develop more and better theories, for without adequate theoretical support, we may do a technically brillant job of solving the wrong problems. However, the interdisciplinary nature of what information science is becoming means we must use a metatheory to guide the development of these theories. Without metatheory we cannot compare or unify the theories. A major statement in such a metatheory is to claim that there are three levels that should be used for information theorizing: casual, macroscopic, and microscopic. Use of these levels, and of the rules they imply, simplifies the evaluation of existing theories by making clear when theories are comparable in a meaningful way and, when they are not comparable, by showing what type of transformations are necessary to make them comparable.
Indexing documents by gedanken experimentation
Authors: Cooper William S.
Published: June 2007

Although it is widely accepted that indexing and cataloging are central to the document and reference retrieval process, there is as yet little unanimity on the issue of how these operations ought to be carried out. Since indexing is a decision‐making process, decision theory and utility theory have been proposed as a possible theoretical framework within which to formulate decision rules for indexing. These decision rules may be interpreted operationally as guides to the thought processes appropriate to the making of sound indexing decisions. One such thought process involves “gedanken experimentation,” in which the indexer is led to an indexing decision by performing suitable thought experiments. This approach to indexing, in addition to providing a theoretical basis for what the indexer does, lends itself to various training schemes for the education of indexers, to the provision of graphic aids to indexing, and to the evaluation of indexing performance. There are also ramifications for automatic indexing.
Education for information science as a profession
Authors: Swanson Rowena Weiss
Published: June 2007

This paper relates factors pertaining to the development of professional education programs to the current status of education for information science. Information science education has not yet matured to the level of being articulated in a program plan representing the consensus of members of the profession. Components of curriculum plans are discussed. A topic inventory for information science is presented with indications of its utility in curriculum design and assessment. The author advocates that collective action be undertaken by the information science community to formulate a curriculum plan to orient educators, prospective students, and present and prospective clienteles.