bluuebunny/crossref_metadata_2025 huggingface dataset:
Aspirin or Anticoagulants in Stenosis of the Middle Cerebral Artery:A Randomized Trial
Authors: Martí-Fàbregas J. , Cocho D. , Martí-Vilalta J.-L. , Gich I. , Belvís R. , Bravo Y. , Millán M. , Castellanos M. , Rodríguez-Campello A. , Egido J. , Geffner D. , Gil-Núñez A. , Marta J. , Navarro R. , Obach V. , Palomeras E.
Published: May 2006

Background: We report the results of an open, randomized, multicenter trial that compared the efficacy of aspirin to oral anticoagulants (OA) for the prevention of vascular events in patients with symptomatic stenosis of the middle cerebral artery (MCA). Methods: Participants were randomly assigned to receive 300 mg/day of aspirin or a dose of OA (target INR 2–3). The MCA stenosis was demonstrated by conventional angiography or by at least two noninvasive examinations. Patients had either transient ischemic attack or cerebral infarct (CI) attributable to the MCA stenosis within 90 days before inclusion. The primary endpoint was: nonfatal CI, nonfatal acute myocardial infarct, vascular death and major hemorrhage. The patients were followed-up for a minimum of 1 year and a maximum of 3 years. Results: The study included 28 patients (14 in each treatment group); the average age was 67 ± 9.9 years. Men constituted 68% of the patients. After a mean follow-up of 23.1 ± 10.9 months, there were no recurrences of CI in both groups. No endpoint was reported in the aspirin group, but 2 patients in the OA group (14.3%) exhibited vascular events: 1 acute myocardial infarct and 1 intracerebral hemorrhage). However, this difference was not statistically significant (p = 0.48). Conclusions: Our study suggests that aspirin is the treatment of choice for the prevention of vascular events in patients with symptomatic MCA stenosis.
Dementia in Subjects Aged 75 Years or Over within the PAQUID Cohort: Prevalence and Burden by Severity
Authors: Helmer Catherine , Pérès Karine , Letenneur Luc , Guttiérez-Robledo Luis Miguel , Ramaroson Hanta , Barberger-Gateau Pascale , Fabrigoule Colette , Orgogozo Jean-Marc , Dartigues Jean-François
Published: May 2006

Background/Aims: To analyze the prevalence of dementia by severity and to describe the sociodemographic characteristics of people with dementia in the community, as well as the consequences of this disease in terms of disability and institutionalization. Methods: This study was based on the PAQUID community-based cohort study of 1,461 subjects aged 75 years or over. Severity of dementia was assessed using the Mini-Mental State Examination (MMSE). Results: The prevalence of dementia was estimated to be 17.8%, with about 43% at a moderately severe or more severe stage of the disease (MMSE ≤ 15). About 39% of the people with dementia lived in an institution. Among the institutionalized residents, 71.6% were diagnosed as demented. About 57% of the people with dementia were ADL disabled. In this over-75 population, people with dementia accounted for 74% of the ADL-disabled subjects. The consequences of dementia were particularly frequent among the subjects who were at least at a moderately severe stage of dementia, with 59.6% of them living in institution and 87.2% being ADL disabled. Conclusion: These results confirm the high prevalence of dementia in subjects aged over 75 and illustrate the devastating consequences of this disease in terms of disability and institutionalization.
Association of Polymorphism in the Transcription Factor LBP-1c/CP2/LSF Gene with Alzheimer’s Disease and Major Depression
Authors: Schahab Schamim , Heun Reinhard , Schmitz Sandra , Maier Wolfgang , Kölsch Heike
Published: May 2006

The transcription factor LBP-1c/CP2/LSF (LBP-1c) is a candidate gene for Alzheimer’s disease (AD) because it is located in a putative hotspot for an AD risk gene on chromosome 12. We investigated the effect of LBP-1c polymorphism on the risk of AD in 162 AD patients, 180 patients with major depression as hospitalized controls and 225 healthy subjects. We observed no significant association of the LBP-1c A allele with AD. Nor did we detect an interaction of the LBP-1c A allele with the apolipoprotein E4 (ApoE4) allele or the low-density lipoprotein receptor-related protein T allele which could have been related to the risk of AD. However, exploratory data analysis revealed that the LBP-1c A allele might act as a protective factor in major depression. A recent study also described an association of another gene located on chromosome 12, the mannose 6-phosphatase receptor gene, with major depression. These data suggest the presence of a putative risk gene for major depression at chromosome 12.
Enhanced Expression of Serum and Glucocorticoid-Inducible Kinase-1 in Kidneys of L-NAME-Treated Rats
Authors: Feng Yuxi , Wang Yumei , Xiong Jing , Liu Zhenzi , Yard Benito , Lang Florian
Published: May 2006

Objective: The serum and glucocorticoid-inducible kinase-1 (SGK1) has previously been shown to be highly expressed in renal injury such as glomerulonephritis and diabetic nephropathy. Inhibition of nitric oxide synthase with NG-nitro-L-arginine methyl ester (L-NAME) leads to arterial hypertension with subsequent renal injury. The present study explored whether chronic treatment with L-NAME affected renal SGK1 expression. Methods: 36 Sprague-Dawley rats were divided into a control group and an experimental group, in which hypertension was induced by oral administration of L-NAME (100 mg/kg/day). The rats were sacrificed 4 and 8 weeks, respectively, after initiation of the treatment. Blood pressure was determined with the tail-cuff method, urinary albumin and β2-microglobulin concentration were measured using an immunoturbidimetric assay, and SGK1 expression in renal cortex was quantified by real-time PCR and Western blotting. Results: The administration of L-NAME increased systolic blood pressure significantly from 107 to 135 mm Hg within 4 weeks and to 155 mm Hg within 8 weeks. It further enhanced urinary excretion of albumin and β2-microglobulin. Histology revealed marked fibrosis of glomerular and tubular tissue. The 4- and 8-week L-NAME treatment increased significantly (p < 0.01) SGK1 mRNA and protein abundance in renal cortex. Conclusions:L-NAME treatment leads to hypertension, proteinuria and renal fibrosis. It increases renal transcription and expression of SGK1, which has previously been shown to foster matrix protein deposition and could thus contribute to renal injury.
Fat Intake at Midlife and Risk of Dementia and Alzheimer’s Disease: A Population-Based Study
Authors: Laitinen M.H. , Ngandu T. , Rovio S. , Helkala E.-L. , Uusitalo U. , Viitanen M. , Nissinen A. , Tuomilehto J. , Soininen H. , Kivipelto M.
Published: May 2006

Background: Lifestyle and vascular factors have been linked to dementia and Alzheimer’s disease (AD), but the role of dietary fats in the development of dementia is less clear. Methods: Participants were derived from random, population-based samples initially studied in midlife (1972, 1977, 1982, or 1987). Fat intake from spreads and milk products was assessed using a structured questionnaire and an interview. After an average follow-up of 21 years, a total of 1,449 (73%) individuals aged 65–80 years participated in the re-examination in 1998. Altogether 117 persons had dementia. Results: Moderate intake of polyunsaturated fats at midlife decreased the risk of dementia even after adjustment for demographic variables, other subtypes of fats, vascular risk factors and disorders, and apolipoprotein E (ApoE) genotype (OR 0.40, CI 0.17–0.94 for the 2nd quartile vs. 1st quartile), whereas saturated fat intake was associated with an increased risk (OR 2.45, CI 1.10–5.47 for the 2nd quartile). The associations were seen only among the ApoE Ε4 carriers. Conclusions: Moderate intake of unsaturated fats at midlife is protective, whereas a moderate intake of saturated fats may increase the risk of dementia and AD, especially among ApoE Ε4 carriers. Thus, dietary interventions may potentially modify the risk of dementia, particularly among genetically susceptible individuals.
Augmentation of Proliferation of Vascular Smooth Muscle Cells by Plasminogen Activator Inhibitor Type 1
Authors: Chen Yabing , Budd Ralph C. , Kelm Robert J. , Sobel Burton E. , Schneider David J.
Published: May 2006

Objective—Proliferation of vascular smooth muscle cells (VSMCs) contributes to restenosis after coronary intervention. We have shown previously that increased expression of plasminogen activator inhibitor type 1 (PAI-1) limits VSMC apoptosis. Because apoptosis and proliferation appear to be linked, we sought to determine whether increased PAI-1 would affect VSMC proliferation.

Methods and Results—VSMCs were explanted from control and transgenic mice (SM22-PAI+) in which VSMC expression of PAI-1 was increased. Increased growth of SM22-PAI+-VSMCs (2.3±0.4-fold) reflected, at least partially, increased proliferation. Greater expression of FLICE-like inhibitory protein (FLIP; 2.7-fold) and its cleaved active form were seen in SM22-PAI+-VSMCs. The balance between caspase-8 and FLIP favored proliferation in SM22-PAI+-VSMCs. Increased expression of NF-κB and activation of extracellular signal-regulated kinase (ERK) were demonstrated in SM22-PAI+-VSMCs (fold=NF-κB=2.2±0.1, fold=phosphorylated-ERK=1.6±0.1). Results were confirmed when expression of PAI-1 was increased by transfection. Inhibition of NF-κB and ERK attenuated proliferation in SM22-PAI+-VSMCs. Increased expression of PAI-1 promoted proliferation when VSMCs were exposed to tumor necrosis factor (TNF).

Conclusions—Increased expression of PAI-1 is associated with greater activity of FLIP that promotes VSMC proliferation through NF-κB and ERK. Thus, when vascular wall expression of PAI-1 is increased, restenosis after coronary intervention is likely to be potentiated by greater proliferation of VSMC and resistance to apoptosis.
An Osteopontin–NADPH Oxidase Signaling Cascade Promotes Pro–Matrix Metalloproteinase 9 Activation in Aortic Mesenchymal Cells
Authors: Lai Chung-Fang , Seshadri Venkat , Huang Kane , Shao Jian-Su , Cai Jun , Vattikuti Radhika , Schumacher Arwyn , Loewy Arleen P. , Denhardt David T. , Rittling Susan R. , Towler Dwight A.
Published: May 2006

Osteopontin (OPN) is a cytokine upregulated in diabetic vascular disease. To better understand its role in vascular remodeling, we assessed how OPN controls metalloproteinase (MMP) activation in aortic adventitial myofibroblasts (AMFs) and A7r5 vascular smooth muscle cells (VSMCs). By zymography, OPN and tumor necrosis factor (TNF)-α preferentially upregulate pro–matrix metalloproteinase 9 (pro-MMP9) activity. TNF-α upregulated pro-MMP9 in AMFs isolated from wild-type (OPN
+/+
) mice, but pro-MMP9 induction was abrogated in AMFs from OPN
−/−
mice. OPN treatment of VSMCs enhanced pro-MMP9 activity, and TNF-α induction of pro-MMP9 was inhibited by anti-OPN antibody and apocynin. Superoxide and the oxylipid product 8-isoprostaglandin F
2
α-isoprostane (8-IsoP) were increased by OPN treatment, and anti-OPN antibody suppressed 8-IsoP production. Like OPN and TNF-α, 8-IsoP preferentially activated pro-MMP9. Superoxide, 8-IsoP, and NADPH oxidase 2 (Nox2) subunits were reduced in OPN
−/−
AMFs. Treatment of A7r5 VSMCs with OPN upregulated NADPH oxidase subunit accumulation. OPN structure/function studies mapped these activities to the SVVYGLR heptapeptide motif in the thrombin-liberated human OPN N-terminal domain (SLAYGLR in mouse OPN). Treatment of aortic VSMCs with SVVYGLR upregulated pro-MMP9 activity and restored TNF-α activation of pro-MMP9 in OPN
−/−
AMFs. Injection of OPN-deficient OPN
+/−
mice with SVVYGLR peptide upregulated pro-MMP9 activity, 8-IsoP levels, and Nox2 protein levels in aorta and increased panmural superoxide production (dihydroethidium staining). At equivalent hyperglycemia and dyslipidemia, 8-IsoP levels and aortic pro-MMP9 were reduced with complete OPN deficiency in a model of diet-induced diabetes, achieved by comparing OPN
−/−
/LDLR
−/−
versus OPN
+/−
/LDLR
−/−
siblings. Thus, OPN provides a paracrine signal that augments vascular pro-MMP9 activity, mediated in part via superoxide generation and oxylipid formation.
Selectivity of Connexin 43 Channels Is Regulated Through Protein Kinase C–Dependent Phosphorylation
Authors: Ek-Vitorin Jose F. , King Timothy J. , Heyman Nathanael S. , Lampe Paul D. , Burt Janis M.
Published: May 2006

Coordinated contractile activation of the heart and resistance to ischemic injury depend, in part, on the intercellular communication mediated by Cx43-composed gap junctions. The function of these junctions is regulated at multiple levels (assembly to degradation) through phosphorylation at specific sites in the carboxyl terminus (CT) of the Cx43 protein. We show here that the selective permeability of Cx43 junctions is regulated through protein kinase C (PKC)-dependent phosphorylation at serine 368 (S368). Selective permeability was measured in several Cx43-expressing cell lines as the rate constant for intercellular dye diffusion relative to junctional conductance. The selective permeability of Cx43 junctions under control conditions was quite variable, as was the open-state behavior of the comprising channels. Coexpression of the CT of Cx43 as a distinct protein, treatment with a PKC inhibitor, or mutation of S368 to alanine, all reduced (or eliminated) phosphorylation at S368, reduced the incidence of 55- to 70-pS channels, and reduced by 10-fold the selective permeability of the junctions for a small cationic dye. Because PKC activation during preischemic conditioning is cardioprotective during subsequent ischemic episodes, we examined no-flow, ischemic hearts for Cx43 phosphorylated at S368 (pS368). Consistent with early activation of PKC, pS368-Cx43 was increased in ischemic hearts; despite extensive lateralization of total Cx43, pS368-Cx43 remained predominantly at intercalated disks. Our data suggest that the selectivity of gap junction channels at intercalated disks is increased early in ischemia.
Seasonality and Meridional Propagation of the MJO
Authors: Wu Man-Li C. , Schubert Siegfried D. , Suarez Max J. , Pegion Philip J. , Waliser Duane E.
Published: May 2006

The Madden–Julian oscillation (MJO) is known to have a substantial impact on the variability of the Asian–Australian summer monsoons. An important, but not well understood, aspect of the MJO–monsoon connection is the meridional propagation of bands of enhanced or reduced precipitation that are especially pronounced during the northern summer. In this study, the nature of the seasonality of the MJO is examined, with a focus on the meridional propagation, using both observations and simulations with an atmospheric general circulation model (AGCM).

A key result is that the AGCM, when forced with idealized eastward propagating equatorial dipole heating anomalies, reproduces the salient features of the observed seasonality in the precipitation and wind fields associated with the MJO, including meridional propagation into the Indian and Australian summer monsoon regions. An analysis of the simulations and observations shows that the off-equatorial precipitation anomalies are initiated by surface frictional convergence/divergence associated with the Rossby wave response to the leading pole of the equatorial heating dipole. The off-equatorial precipitation anomalies develop further by interacting with the trailing pole of the equatorial dipole heating to produce a northwest–southeast (or southwest–northeast) oriented line of surface convergence/divergence that propagates to the east. Since the prescribed heating does not vary by season, the seasonal asymmetry in the response must be the result of the seasonal changes in the background state. In particular, the results suggest that seasonal changes in both the vertical wind shear and static stability play a role.
Preferred Modes of Variability and Their Relationship with Climate Change
Authors: Son Seok-Woo , Lee Sukyoung
Published: May 2006

Spatial structure of annular modes shows a remarkable resemblance to that of the recent trend in the observed circulation (Thompson et al.). This study performs a series of multilevel primitive equation model simulations to examine the extent to which the annular mode is capable of predicting changes in the zonal-mean flow response to external heat perturbations. Each of these simulations represents a statistically steady state and differs from each other in the values of the imposed tropical heating (ℋ) and high-latitude cooling (𝒞).

Defining the annular mode as the first empirical orthogonal function (EOF1) of zonal-mean tropospheric zonal wind, it is found that the “climate predictability” is generally high in the small 𝒞–large ℋ region of the parameter space, but is markedly low in the large 𝒞–small ℋ region. In the former region, EOF1 represents meridional meandering of the midlatitude jet, while in the latter region, EOF1 and EOF2 combine to represent coherent poleward propagation of zonal-mean flow anomalies. It is also found that the climate predictability tends to be higher with respect to changes in 𝒞 than to changes in ℋ. The implications of these findings for the Southern Hemisphere climate predictability are also presented.
An Operational Dynamical Downscaling Prediction System for Nordeste Brazil and the 2002–04 Real-Time Forecast Evaluation
Authors: Sun Liqiang , Li Huilan , Zebiak Stephen E. , Moncunill David F. , Filho Francisco D. A. D. S. , Moura Antonio D.
Published: May 2006

The International Research Institute for Climate Prediction (IRI) and Ceará Foundation for Meteorology and Water Resources (FUNCEME) in Brazil have developed a dynamical downscaling prediction system for Northeast Brazil (the Nordeste) and have been issuing seasonal rainfall forecasts since December 2001. To the authors’ knowledge, this is the first operational climate dynamical downscaling prediction system. The ECHAM4.5 AGCM and the NCEP Regional Spectral Model (RSM) are the core of this prediction system. This is a two-tiered prediction system. SST forecasts are produced first, which then serve as the lower boundary condition forcing for the ECHAM4.5 AGCM–NCEP RSM nested system. Hindcasts for January–June 1971–2000 with the nested model, using observed SSTs, provided estimates of model potential predictability and characteristics of the model climatology. During 2002–04, the overall rainfall forecast skill, measured by the ranked probability skill score (RPSS), is positive over a majority of the Nordeste. Higher skill is found for the March–May (MAM) and April–June (AMJ) seasons with forecast lead times up to 3 months. The skill of the downscaled forecasts is generally higher than that of the driving global model forecasts.
Biases in Stratospheric and Tropospheric Temperature Trends Derived from Historical Radiosonde Data
Authors: Randel William J. , Wu Fei
Published: May 2006

Temperature trends derived from historical radiosonde data often show substantial differences compared to satellite measurements. These differences are especially large for stratospheric levels, and for data in the Tropics, where results are based on relatively few stations. Detailed comparisons of one radiosonde dataset with collocated satellite measurements from the Microwave Sounding Unit reveal time series differences that occur as step functions or jumps at many stations. These jumps occur at different times for different stations, suggesting that the differences are primarily related to problems in the radiosonde data, rather than in the satellite record. As a result of these jumps, the radiosondes exhibit systematic cooling biases relative to the satellites. A large number of the radiosonde stations in the Tropics are influenced by these biases, suggesting that cooling in the tropical lower stratosphere is substantially overestimated in these radiosonde data. Comparison of trends from stations with larger and smaller biases suggests the cooling bias extends into the tropical upper troposphere. Significant biases are observed in both daytime and nighttime radiosonde measurements.
Seasonal and El Niño Variability in Weekly Satellite Evaporation over the Global Ocean during 1996–98
Authors: Mestas-Nuñez Alberto M. , Bentamy Abderrahim , Katsaros Kristina B.
Published: May 2006

The seasonal and anomaly variability of satellite-derived weekly latent heat fluxes occurring over the global oceans during a 3-yr period (January 1996–December 1998) is investigated using EOF and harmonic analyses. The seasonal cycle of latent heat flux is estimated by least squares fitting the first three (annual, semiannual, and 4 month) harmonics to the data. The spatial patterns of amplitudes of these harmonics agree well with the corresponding patterns for wind speed. The annual harmonic captures an oscillation that reflects high evaporation in late fall/early winter and low evaporation in late spring/early summer in both hemispheres, with larger amplitudes in the Northern Hemisphere over the western side of the oceans and significant phase differences within each hemisphere. The main feature of the semiannual harmonic is its large amplitude in the Asian monsoon region (e.g., in the Arabian Sea its amplitude is about 1.5 larger than the annual) and the out-of-phase relationship of this region with the high latitudes of the North Pacific, consistent with other studies. The third harmonic shows three main regions with relatively large amplitudes, one in the Arabian Sea and two out-of-phase regions in the central midlatitude North and South Pacific. After removing this estimate of the seasonal cycle from the data, the leading EOF of the anomalies isolates the 1997–98 El Niño signal, with enhanced evaporation in the eastern tropical Pacific, around the Maritime Continent, in the midlatitude North and South Pacific, and the equatorial Indian Ocean, and reduced evaporation elsewhere around the global ocean during April 1997–April 1998. This pattern is consistent with known patterns of ENSO variability and with the “atmospheric bridge” teleconnection concept. The current study illustrates the usefulness of satellite-derived latent heat fluxes for climatic applications.
Forecasting Nationwide Demand for the Cardiac PTCA Procedure
Authors: Amar Sundeep , Srivastava Sundeep , Vaid Vineet , Mahajan Siddharth
Published: May 2006

The PTCA procedure or angioplasty is a major strategy in the treatment of Coronary Artery Disease. In this article, we forecast the demand for PTCA procedures on a monthly basis using past data. There are a total of 80 hospitals in the country wherein PTCA procedures are currently performed. Of these, data was collected for 21 hospitals in the North and East on the number of PTCA procedures performed from January 2003 to June 2004, for a period of 18 months. Based on volumes of procedures performed, the hospitals were divided into 8 segments. Forecasting of demand was done for each segment and then the segment level forecasts were combined to give an overall forecast for the next month, i.e., July 2004. The forecasting procedure is based on two methods, Exponential Smoothing and Exponential Smoothing with Trend (Holt's Method).
State of Organizational Culture for Knowledge Management in Indian Industry
Authors: Pillania Rajesh K.
Published: May 2006

We are in the knowledge economy and management scholars worldwide agree that knowledge is the most critical resource today. Organizational culture is highlighted as the major reason behind failure of knowledge management initiatives. I conducted research to understand the current state of organizational culture for knowledge management in the selected sectors of software, pharmaceuticals and petroleum marketing, taking into account both macro and micro aspects in both private and public sectors. The findings are not very encouraging as they reveal that there is a lack of organizational culture for knowledge creation, sharing and dissemination which has serious implications for the competitiveness of the firms, industry and the country.
Guarding Privacy on the Internet
Authors: Bhasin Madan Lal
Published: May 2006

Undoubtedly, the government, business houses and employers have a legitimate need to collect data and to monitor people, but their practices often threaten an individual's privacy. Since a vast amount of data can be collected on the Internet, and due to its global ramifications, the FTC had identified ‘core’ principles of privacy which are widely accepted by leading countries. With the European Directive in force from 1998, ‘trust seals’ and ‘government regulations’ are the two leading forces pushing for more privacy disclosures. The need for companies to develop and put into place good privacy policies and/or statements has become more crucial than ever.

Privacy legislation prevalent in the US, the EU, Canada, Japan and Australia is summarized in this article. Privacy laws vary throughout the globe but, unfortunately, the topic has turned out to be the subject of legal contention between the EU and the US. Among the companies given high marks by privacy advocates for making data protection a priority are Dell, IBM, Intel, Microsoft, Procter & Gamble, Time Warmer and Verizon.

Currently, the only way consumers can stop the collection of their personal data is to ‘opt-out’ or configure the browser to reject ‘cookies’. We have briefly examined various methods (like Carnivore program, W3C Platform for Privacy Preferences (P3P), Encryption, etc.) used by the corporate world. Today, more advanced technological safeguards are needed. For corporations that collect and use personal information, ignoring privacy legislative and regulatory warning signs can prove to be a costly mistake.
Klauch International*
Authors: Mohan T.R. Madan , Dutta Shantanu
Published: May 2006

The case deals with entry and location decisions and project attractiveness evaluation of Klauch International into the Bangladesh Cement industry. While demand for cement is on the rise in Bangladesh, the resource constraints bring unique challenges to the project, such as creations of subsidiaries across borders to ‘signal’ and buy legitimacy of the project from different stakeholders. Klauch is evaluating the financial, market and political risks involved.
NPM-ALK–dependent expression of the transcription factor CCAAT/enhancer binding protein β in ALK-positive anaplastic large cell lymphoma
Authors: Quintanilla-Martinez Leticia , Pittaluga Stefania , Miething Cornelius , Klier Margit , Rudelius Martina , Davies-Hill Theresa , Anastasov Natasa , Martinez Antonio , Vivero Angelica , Duyster Justus , Jaffe Elaine S. , Fend Falko , Raffeld Mark
Published: May 2006

CCAAT/enhancer binding protein β (C/EBPβ) is one of a 6-member family of C/EBPs. These transcription factors are involved in the regulation of various aspects of cellular growth and differentiation. Although C/EBPβ has important functions in B- and T-cell differentiation, its expression has not been well studied in lymphoid tissues. We, therefore, analyzed its expression by immunohistochemistry and Western blot in normal lymphoid tissues and in 248 well-characterized lymphomas and lymphoma cell lines. Nonneoplastic lymphoid tissues and most B-cell, T-cell, and Hodgkin lymphomas lacked detectable levels of C/EBPβ. In contrast, most (40 of 45; 88%) cases of ALK-positive anaplastic large cell lymphoma (ALCL) strongly expressed C/EBPβ. Western blot analysis confirmed C/EBPβ expression in the ALK-positive ALCLs and demonstrated elevated levels of the LIP isoform, which has been associated with increased proliferation and aggressiveness in carcinomas. Transfection of Ba/F3 and 32D cells with NPM-ALK and a kinase-inhibitable modified NPM-ALK resulted in the induction of C/EBPβ and demonstrated dependence on NPM-ALK kinase activity. In conclusion, we report the constitutive expression of C/EBPβ in ALK-positive ALCL and show its relationship to NPM-ALK. We suggest that C/EBPβ is likely to play an important role in the pathogenesis and unique phenotype of this lymphoma.
Inhibition of RhoA GTPase activity enhances hematopoietic stem and progenitor cell proliferation and engraftment
Authors: Ghiaur Gabriel , Lee Andrew , Bailey Jeff , Cancelas Jose A. , Zheng Yi , Williams David A.
Published: May 2006

Ras-related Rho GTPases regulate actin cytoskeletal organization, adhesion, gene transcription, and cell-cycle progression. The Rac subfamily of Rho GTPases and Cdc42 has been shown to play essential roles in hematopoietic stem cell (HSC) engraftment and mobilization. Here, we study the role of RhoA, a related Rho GTPase, in HSC functions. Using retrovirus-mediated gene transfer of a dominant-negative (DN) mutant of RhoA (RhoAN19), we demonstrate that down-regulation of RhoA activity resulted in increased HSC engraftment and self-renewal as measured by competitive repopulation and serial transplantation assays. However, overexpression of RhoAN19 resulted in decreased migration toward SDF-1α and α4β1- and α5β2-integrin–mediated adhesion of hematopoietic progenitor cells in vitro. Low RhoA activity was associated with higher proliferation rate of hematopoietic progenitor cells and increased cells in active phases of cell cycle, most likely via decreasing p21Cip/Waf expression and increasing cyclin D1 levels. Thus, reducing RhoA activity by optimizing the balance between adhesion/migration and proliferation/self-renewal results in a net increase in HSC engraftment. This mechanism could provide a novel therapeutic target to enhance HSC therapies.
Empirical array quality weights in the analysis of microarray data
Authors: Ritchie Matthew E , Diyagama Dileepa , Neilson Jody , van Laar Ryan , Dobrovic Alexander , Holloway Andrew , Smyth Gordon K
Published: May 2006

Background

Assessment of array quality is an essential step in the analysis of data from microarray experiments. Once detected, less reliable arrays are typically excluded or "filtered" from further analysis to avoid misleading results.

Results

In this article, a graduated approach to array quality is considered based on empirical reproducibility of the gene expression measures from replicate arrays. Weights are assigned to each microarray by fitting a heteroscedastic linear model with shared array variance terms. A novel gene-by-gene update algorithm is used to efficiently estimate the array variances. The inverse variances are used as weights in the linear model analysis to identify differentially expressed genes. The method successfully assigns lower weights to less reproducible arrays from different experiments. Down-weighting the observations from suspect arrays increases the power to detect differential expression. In smaller experiments, this approach outperforms the usual method of filtering the data. The method is available in the limma software package which is implemented in the R software environment.

Conclusion

This method complements existing normalisation and spot quality procedures, and allows poorer quality arrays, which would otherwise be discarded, to be included in an analysis. It is applicable to microarray data from experiments with some level of replication.
Differential cognitive impairment for diverse forms of multiple sclerosis
Authors: Gonzalez-Rosa Javier J , Vazquez-Marrufo Manuel , Vaquero Encarnacion , Duque Pablo , Borges Monica , Gamero Miguel A , Gomez Carlos M , Izquierdo Guillermo
Published: May 2006

Background

Cognitive impairment is a common feature in multiple sclerosis (MS) patients and occurs in 60% of all cases. Unfortunately, neurological examination does not always agree with the neuropsychological evaluation in determining the cognitive profile of the patient. On the other hand, psychophysiological techniques such as event-related potentials (ERPs) can help in evaluating cognitive impairment in different pathologies.

Behavioural responses and EEG signals were recorded during the experiment in three experimental groups: 1) a relapsing-remitting group (RRMS), 2) a benign multiple sclerosis group (BMS) and 3) a Control group. The paradigm employed was a spatial attention task with central cues (Posner experiment). The main aim was to observe the differences in the performance (behavioural variables) and in the latency and amplitude of the ERP components among these groups.

Results

Our data indicate that both MS groups showed poorer task performance (longer reaction times and lower percentage of correct responses), a latency delay for the N1 and P300 component, and a different amplitude for the frontal N1. Moreover, the deficit in the BMS group, indexed by behavioural and pyschophysiological variables, was more pronounced compared to the RRMS group.

Conclusion

The present results suggest a cognitive impairment in the information processing in all of these patients. Comparing both pathological groups, cognitive impairment was more accentuated in the BMS group compared to the RMSS group. This suggests a silent deterioration of cognitive skills for the BMS that is not usually treated with pharmacological or neuropsychological therapy.
Adrenalectomy promotes a permanent decrease of plasma corticoid levels and a transient increase of apoptosis and the expression of Transforming Growth Factor β1 (TGF-β1) in hippocampus: effect of a TGF-β1 oligo-antisense
Authors: Bravo Javier A , Parra Claudio S , Arancibia Sandor , Andrés Sergio , Morales Paola , Herrera-Marschitz Mario , Herrera Luisa , Lara Hernán E , Fiedler Jenny L
Published: May 2006

Background

Corticosterone reduction produced by adrenalectomy (ADX) induces apoptosis in dentate gyrus (DG) of the hippocampus, an effect related to an increase in the expression of the pro-apoptotic gene bax. However it has been reported that there is also an increase of the anti-apoptotic gene bcl-2, suggesting the promotion of a neuroprotective phenomenon, perhaps related to the expression of transforming growth factor β1 (TGF-β1). Thus, we have investigated whether TGF-β1 levels are induced by ADX, and whether apoptosis is increased by blocking the expression of TGF-β1 with an antisense oligonucleotide (ASO) administered intracerebrally in corticosterone depleted rats.

Results

It was observed an increase of apoptosis in DG, 2 and 5 days after ADX, in agreement with a reduction of corticosterone levels. However, the effect of ADX on the number of apoptotic positive cells in DG was decreased 5 days after the lesion. In CA1–CA3 regions, the effect was only observed 2 days after ADX. TGF-β1 mRNA levels were increased 2 days after ADX. The sustained intracerebro-ventricular administration of a TGF-β1 ASO via an osmotic mini pump increased apoptosis levels in CA and DG regions 5 days after ADX as well as sham-operated control animals. No significant effect was observed following a scrambled-oligodeoxynucleotide treatment.

Conclusion

The changes in both the pattern and the magnitude of apoptotic-cell morphology observed 2 and 5 days after ADX suggest that, as a consequence of the reduction of corticosteroids, some trophic mechanisms restricting cell death to a particular time window are elicited. Sustained intracerebral administration of TGF-β1 ASO increased the apoptosis promoted by ADX, suggesting that TGF-β1 plays an anti-apoptotic role in vivo in hippocampus.
Procalcitonin is not sufficiently reliable to be the sole marker of neonatal sepsis of nosocomial origin
Authors: López Sastre José B , Pérez Solís David , Roqués Serradilla Vicente , Fernández Colomer Belén , Coto Cotallo Gil D , Krauel Vidal Xavier , Narbona López Eduardo , García del Río Manuel , Sánchez Luna Manuel , Belaustegui Cueto Antonio , Moro Serrano Manuel , Urbón Artero Alfonso , Álvaro Iglesias Emilio , Cotero Lavín Ángel , Martínez Vilalta Eduardo , Jiménez Cobos Bartolomé ,   "Grupo de Hospitales Castrillo"
Published: May 2006

Background

It has recently been suggested that serum procalcitonin (PCT) is of value in the diagnosis of neonatal sepsis, with varying results. The aim of this prospective multicenter study was to assess the usefulness of PCT as a marker of neonatal sepsis of nosocomial origin.

Methods

One hundred infants aged between 4 and 28 days of life admitted to the Neonatology Services of 13 acute-care teaching hospitals in Spain over 1-year with clinical suspicion of neonatal sepsis of nosocomial origin were included in the study. Serum PCT concentrations were determined by a specific immunoluminometric assay. The reliability of PCT for the diagnosis of nosocomial neonatal sepsis at the time of suspicion of infection and at 12–24 h and 36–48 h after the onset of symptoms was calculated by receiver-operating characteristics (ROC) curves. The Youden's index (sensitivity + specificity - 1) was used for determination of optimal cutoff values of the diagnostic tests in the different postnatal periods. Sensitivity, specificity, and the likelihood ratio of a positive and negative result with the 95% confidence interval (CI) were calculated.

Results

The diagnosis of nosocomial sepsis was confirmed in 61 neonates. Serum PCT concentrations were significantly higher at initial suspicion and at 12–24 h and 36–48 h after the onset of symptoms in neonates with confirmed sepsis than in neonates with clinically suspected but not confirmed sepsis. Optimal PCT thresholds according to ROC curves were 0.59 ng/mL at the time of suspicion of sepsis (sensitivity 81.4%, specificity 80.6%); 1.34 ng/mL within 12–24 h of birth (sensitivity 73.7%, specificity 80.6%), and 0.69 ng/mL within 36–48 h of birth (sensitivity 86.5%, specificity 72.7%).

Conclusion

Serum PCT concentrations showed a moderate diagnostic reliability for the detection of nosocomial neonatal sepsis from the time of suspicion of infection. PCT is not sufficiently reliable to be the sole marker of sepsis, but would be useful as part of a full sepsis evaluation.
The impact of clothing style on bone mineral density among post menopausal women in Morocco: a case-control study
Authors: Allali Fadoua , Aichaoui Siham El , Saoud Bouchra , Maaroufi Houda , Abouqal Redouane , Hajjaj-Hassouni Najia
Published: May 2006

Background

The clothing style is an important factor that influences vitamin D production and thus bone mineral density. We performed a case-control study in order to evaluate the effect of veil wearing (concealing clothing) on bone mineral density in Moroccan post menopausal women.

Methods

The cases were osteoporotic women whose disease was assessed by bone mineral density measurement. Each patient was matched with a non osteoporotic woman for age, and body mass index. All our patients were without secondary causes or medications that might affect bone density. The veil was defined as a concealing clothing which covered most of the body including the arms, the legs and the head. This definition is this of the usual Moroccan traditional clothing style.

Results

178 post menopausal osteoporotic patients and 178 controls were studied. The mean age of the cases and the controls was 63.2 years (SD 7) and the mean body mass index was 32.1 (SD 8). The results of crude Odds Ratios analyses indicated that wearing a veil was associated with a high risk of osteoporosis: OR 2.29 (95% CI, 1.38–3.82). Multiparity or a history of familial peripheral osteoporotic fractures had also a significant effect on increasing the osteoporosis risk (ORs: 1.87 (95% CI, 1.05–3.49) and 2.01 (95% CI, 1.20–3.38)). After a multiple regression analysis, wearing the veil and a history of familial osteoporotic fractures remained the both independent factors that increased the osteoporosis risk (ORs: 2.20 (95% CI, 1.22–3.9) and 2.19 (95% CI, 1.12–4.29) respectively).

Conclusion

our study suggested that in Moroccan post menopausal women, wearing a traditional concealing clothing covering arms, legs and head increased the risk of osteoporosis. Further studies are required to evaluate the clinical impact of the above findings and to clarify the status of vitamin D among veiled women in Morocco.
The shortened disabilities of the arm, shoulder and hand questionnaire (Quick DASH): validity and reliability based on responses within the full-length DASH
Authors: Gummesson Christina , Ward Michael M , Atroshi Isam
Published: May 2006

Background

The 30-item disabilities of the arm, shoulder and hand (DASH) questionnaire is increasingly used in clinical research involving upper extremity musculoskeletal disorders. From the original DASH a shorter version, the 11-item Quick DASH, has been developed. Little is known about the discriminant ability of score changes for the Quick DASH compared to the DASH. The aim of this study was to assess the performance of the Quick DASH and its cross-sectional and longitudinal validity and reliability.

Methods

The study was based on extracting Quick DASH item responses from the responses to the full-length DASH questionnaire completed by 105 patients with a variety of upper extremity disorders before surgery and at follow-up 6 to 21 months after surgery. The DASH and Quick DASH scores were compared for the whole population and for different diagnostic groups. For longitudinal construct validity the effect size and standardized response mean were calculated. Analyses with ROC curves were performed to compare the ability of the DASH and Quick DASH to discriminate among patients classified according to the magnitude of self-rated improvement. Cross-sectional and test-retest reliability was assessed.

Results

The mean DASH score was 34 (SD 22) and the mean Quick DASH score was 39 (SD 24) at baseline. For the different diagnostic groups the mean and median Quick DASH scores were higher than the corresponding DASH scores. For the whole population, the mean difference between the Quick DASH and DASH baseline scores was 4.2 (95% CI 3.2–5.3), follow-up scores was 2.6 (1.7–3.4), and change scores was 1.7 (0.6–2.8).

The overall effect size and standardized response mean measured with the DASH and the Quick DASH were similar. In the ROC analysis of change scores among patients who rated their arm status as somewhat or much better and those who rated it as unchanged the difference in the area under the ROC curve for the DASH and Quick DASH was 0.01 (95% CI -0.05–0.07) indicating similar discriminant ability.

Cross-sectional and test-retest reliability of the DASH and Quick DASH were similar.

Conclusion

The results indicate that the Quick DASH can be used instead of the DASH with similar precision in upper extremity disorders.
Lumbar segmental mobility disorders: comparison of two methods of defining abnormal displacement kinematics in a cohort of patients with non-specific mechanical low back pain
Authors: Abbott J Haxby , Fritz Julie M , McCane Brendan , Shultz Barry , Herbison Peter , Lyons Brett , Stefanko Georgia , Walsh Richard M
Published: May 2006

Background

Lumbar segmental rigidity (LSR) and lumbar segmental instability (LSI) are believed to be associated with low back pain (LBP), and identification of these disorders is believed to be useful for directing intervention choices. Previous studies have focussed on lumbar segmental rotation and translation, but have used widely varying methodologies. Cut-off points for the diagnosis of LSR & LSI are largely arbitrary. Prevalence of these lumbar segmental mobility disorders (LSMDs) in a non-surgical, primary care LBP population has not been established.

Methods

A cohort of 138 consecutive patients with recurrent or chronic low back pain (RCLBP) were recruited in this prospective, pragmatic, multi-centre study. Consenting patients completed pain and disability rating instruments, and were referred for flexion-extension radiographs. Sagittal angular rotation and sagittal translation of each lumbar spinal motion segment was measured from the radiographs, and compared to a reference range derived from a study of 30 asymptomatic volunteers. In order to define reference intervals for normal motion, and define LSR and LSI, we approached the kinematic data using two different models. The first model used a conventional Gaussian definition, with motion beyond two standard deviations (2sd) from the reference mean at each segment considered diagnostic of rotational LSMD and translational LSMD. The second model used a novel normalised within-subjects approach, based on mean normalised contribution-to-total-lumbar-motion. An LSMD was then defined as present in any segment that contributed motion beyond 2sd from the reference mean contribution-to-normalised-total-lumbar-motion. We described reference intervals for normal segmental mobility, prevalence of LSMDs under each model, and the association of LSMDs with pain and disability.

Results

With the exception of the conventional Gaussian definition of rotational LSI, LSMDs were found in statistically significant prevalences in patients with RCLBP. Prevalences at both the segmental and patient level were generally higher using the normalised within-subjects model (2.8 to 16.8% of segments; 23.3 to 35.5% of individuals) compared to the conventional Gaussian model (0 to 15.8%; 4.7 to 19.6%). LSMDs are associated with presence of LBP, however LSMDs do not appear to be strongly associated with higher levels of pain or disability compared to other forms of non-specific LBP.

Conclusion

LSMDs are a valid means of defining sub-groups within non-specific LBP, in a conservative care population of patients with RCLBP. Prevalence was higher using the normalised within-subjects contribution-to-total-lumbar-motion approach.
Slow fertilization of stickleback eggs: the result of sexual conflict?
Authors: Bakker Theo CM , Zbinden Marc , Frommen Joachim G , Weiss Alexander , Largiadèr Carlo R
Published: May 2006

Background

The fertilization success in sperm competition in externally fertilizing fish depends on number and quality of sperm. The time delay between sequential ejaculations may further influence the outcome of sperm competition. Such a time interval can load the raffle over fertilization if fertilization takes place very fast. Short fertilization times are generally assumed for externally fertilizing fish such as the three-spined stickleback (Gasterosteus aculeatus). In this pair-spawning fish, territorial males often try to steal fertilizations in nests of neighbouring males. This sneaking behaviour causes sperm competition. Sneakers will only get a share of paternity when eggs are not fertilized immediately after sperm release. Contrary to males, females may be interested in multiple paternity of their clutch of eggs. There thus may be a sexual conflict over the speed of fertilization.

Results

In this study we used two differentin vitrofertilization experiments to assess how fast eggs are fertilized in sticklebacks. We show that complete fertilization takes more than 5 min which is atypically long for externally fertilizing fishes.

Conclusion

This result suggests that the time difference does not imply high costs to the second stickleback male to ejaculate. Slow fertilization (and concomitant prolonged longevity of sperm) may be the result of sexual conflict in which females aimed at complete fertilization and/or multiple paternity.