bluuebunny/crossref_metadata_2025 huggingface dataset:
Serotonin Increases Susceptibility to Pulmonary Hypertension in
BMPR2
-Deficient Mice
Authors: Long Lu , MacLean Margaret R. , Jeffery Trina K. , Morecroft Ian , Yang Xudong , Rudarakanchana Nung , Southwood Mark , James Victoria , Trembath Richard C. , Morrell Nicholas W.
Published: February 2006

Heterozygous germline mutations in the gene encoding the bone morphogenetic protein type II (BMPR-II) receptor underlie the majority (>70%) of cases of familial pulmonary arterial hypertension (FPAH), and dysfunction of BMP signaling has been implicated in other forms of PAH. The reduced disease gene penetrance in FPAH indicates that other genetic and/or environmental factors may also be required for the clinical manifestation of disease. Of these, the serotonin pathway has been implicated as a major factor in PAH pathogenesis. We investigated the pulmonary circulation of mice deficient in BMPR-II (
BMPR2
+/−
mice) and show that pulmonary hemodynamics and vascular morphometry of
BMPR2
+/−
mice were similar to wild-type littermate controls under normoxic or chronic hypoxic (2- to 3-week) conditions. However, chronic infusion of serotonin caused increased pulmonary artery systolic pressure, right ventricular hypertrophy, and pulmonary artery remodeling in
BMPR2
+/−
mice compared with wild-type littermates, an effect that was exaggerated under hypoxic conditions. In addition, pulmonary, but not systemic, resistance arteries from
BMPR2
+/−
mice exhibited increased contractile responses to serotonin mediated by both 5-HT
2
and 5-HT
1
receptors. Furthermore, pulmonary artery smooth muscle cells from
BMPR2
+/−
mice exhibited a heightened DNA synthesis and activation of extracellular signal-regulated kinase 1/2 in response to serotonin compared with wild-type cells. In vitro and in vivo experiments suggested that serotonin inhibits BMP signaling via Smad proteins and the expression of BMP responsive genes. These findings provide the first evidence for an interaction between BMPR-II-mediated signaling and the serotonin pathway, perturbation of which may be critical to the pathogenesis of PAH.
Cerebrovascular Reactivity and Cognitive Decline in Patients With Alzheimer Disease
Authors: Silvestrini Mauro , Pasqualetti Patrizio , Baruffaldi Roberto , Bartolini Marco , Handouk Yasmin , Matteis Maria , Moffa Filomena , Provinciali Leandro , Vernieri Fabrizio
Published: February 2006

Background and Purpose—

The aim of this study was to explore the possible contribution of alterations in cerebral hemodynamics to the evolution of cognitive impairment in patients with Alzheimer disease (AD).

Method—

Fifty-three patients with AD were investigated. The evolution of cognitive decline over 12 months was evaluated by means of changes in Mini Mental State Examination (MMSE) and AD Assessment Scale for Cognition (ADAS-Cog) scores. Demographic characteristics, vascular risk profile, pharmacological treatment, and presence of white matter lesions were assessed at entry. Further, a basal evaluation of cerebrovascular reactivity to hypercapnia was measured with transcranial Doppler ultrasonography using the breath-holding index (BHI).

Results—

Of all the variables considered, both MMSE and ADAS-Cog changes had the highest correlation with BHI, followed by age and diabetes. After subdividing both cognitive measures reductions into bigger and smaller-than-average decline (2 points for MMSE; 5 points for ADAS-Cog), multiple logistic regression indicated BHI as the sole significant predictor of cognitive decline.

Conclusions—

These results show an association between impaired cerebral microvessels functionality and unfavorable evolution of cognitive function in patients with AD. Further research is needed to fully establish whether altered cerebral hemodynamics may be considered an independent factor in sustaining cognitive decline progression or an effect of pathological processes involved in AD.
Carotid Artery Diameter in Men and Women and the Relation to Body and Neck Size
Authors: Krejza Jaroslaw , Arkuszewski Michal , Kasner Scott E. , Weigele John , Ustymowicz Andrzej , Hurst Robert W. , Cucchiara Brett L. , Messe Steven R.
Published: February 2006

Background and Purpose—

To explore relationships among gender, body size, neck size, and the diameters of the common carotid artery (CCA) and internal carotid artery (ICA).

Methods—

Using multivariate regression, the best predictors of sonographic diameters of CCA and ICA were determined based on age, height, weight, body mass index, body surface area, neck circumference, neck length, and blood pressure.

Results—

Measurements were obtained in 500 consecutive patients (age 52±15 years; 61% women). Mean diameters of ICA (4.66±0.78 mm) and CCA (6.10±0.80 mm) in women were significantly smaller than in men: 5.11±0.87 mm and 6.52±0.98 mm, respectively. Sex significantly influenced the diameters after controlling for body size, neck size, age, and blood pressure.

Conclusions—

Carotid arteries are smaller in women even after adjusting for body and neck size, age, and blood pressure.
Predicting Long-Term Independency in Activities of Daily Living After Middle Cerebral Artery Stroke
Authors: Schiemanck Sven K. , Kwakkel Gert , Post Marcel W.M. , Kappelle L. Jaap , Prevo Arie J.H.
Published: February 2006

Background and Purpose—

To investigate whether neuroimaging information has added predictive value compared with clinical information for independency in activities of daily living (ADL) 1 year after stroke.

Methods—

Seventy-five first-ever middle cerebral artery stroke survivors were evaluated in logistic regression analyses. Model 1 was derived on the basis of clinical variables; for model 2, neuroimaging variables were added to model 1. Independent variables were stroke severity (National Institutes of Health Stroke Scale), consciousness (Glasgow Coma Scale), urinary continence, demographic variables (age, gender, relationship, educational level), hospital of admission, and clinical instruments: sitting balance (trunk control test), motor functioning (Motricity Index), and ADL (Barthel Index). Neuroimaging variables, determined on conventional MRI scans, included: number of days to scanning, lesion volume, lesion localization (cortex/subcortex), hemisphere, and the presence of white matter lesions. ADL independency was defined as 19 and 20 points on Barthel Index. Differences in accuracy of prediction of ADL independence between models 1 and 2 were analyzed by comparing areas under the curve (AUC) in a receiver operating characteristic analysis.

Results—

Model 1 contained as significant predictors: age and ADL (AUC 0.84), correctly predicting 77%. In model 2, number of days to scanning, hemisphere, and lesion volume were added to model 1, increasing the AUC from 0.84 to 0.87, accurately predicting 83% of the surviving patients.

Conclusions—

Clinical variables in the second week after stroke are good predictors for independency in ADL 1 year after stroke. Neuroimaging variables on conventional MRI scans do not have added value in long-term prediction of ADL.
Higher Education as Empowerment
Authors: Bruhn Christa
Published: February 2006

Palestinian universities have been a dynamic force across Palestinian communities since their inception under Israeli occupation in the early 1970s. What began as initiatives of private families or religious foundations to provide local access to higher education soon grew into a widespread presence across Palestinian communities that has had a profound impact on Palestinian national identity and the persistence of Palestine as a nation. This study specifically argues that Palestinian universities have provided Palestinian communities with the physical and conceptual space to sustain the nation of Palestine by enabling Palestinians to define and articulate a Palestinian national identity, engage in resistance to the Israeli occupation of Palestine, and build the nation of Palestine in the absence of a Palestinian state. This study considers the case of Palestinian universities in an effort to shed light on what enables the university to consistently contribute to the human experience over time and across space.
In Search of Identity and Legitimation
Authors: Pedersen Jesper Strandgaard , Dobbin Frank
Published: February 2006

In the late 1970s, neoinstitutional and organizational culture theorists challenged prevailing rationalist organizational paradigms by introducing social constructionism to the field of organizations. Despite their common foundation, these approaches built on seemingly contradictory empirical observations. Institutionalists observed that organizations actively copy one another’s practices, resulting in substantial isomorphism, whereas culture theorists observed that organizations institutionalize distinctive cultures comprising practices that set them apart from others. These seemingly contradictory findings reflect processes of organizational identity formation and interorganizational construction of legitimacy as they have evolved since the rise of the corporate form in the 19th century. Formation of identity through uniqueness and construction of legitimacy through uniformity are two sides of the same coin. Research on management schools suggests organizations pursue individuation through uniqueness and legitimacy through commonality simultaneously and that organizations bridge the two processes in four ways, which the authors dub imitation, hybridization, transmutation, and immunization.
Hybrid Forms and the Evolution of Thrifts
Authors: Haveman Heather A. , Rao Hayagreeva
Published: February 2006

This article assesses the role of hybrid organizational forms in the coevolution of institutions and organizations. The hybrids the authors study combined elements of one basic plan with another; they developed because blending mechanisms between organizational forms were stronger than segregating mechanisms. The existence of hybrids allowed elements of one theory of thrift, embodied in one organizational form, to be slowly dismantled and elements of a new theory, embodied in a different organizational form, to be established gradually rather than abruptly. Thus, the presence of hybrid forms in this organizational population affected both the mode and pace of organizational and institutional coevolution.
Absence of Food Effect on the Pharmacokinetics of Telbivudine Following Oral Administration in Healthy Subjects
Authors: Zhou Xiao‐Jian , Lloyd Deborah M. , Chao George C. , Brown Nathaniel A.
Published: February 2006

The influence of food on the pharmacokinetics of telbivudine, a candidate antiviral agent against hepatitis B virus (HBV), was investigated in healthy adult subjects following a 600‐mg oral dose administered with and without a high‐fat/high‐calorie meal. Telbivudine was well tolerated under fasting and fed conditions. Oral absorption of telbivudine as measured by maximum plasma concentration (Cmax), time to reach Cmax (Tmax), and area under the plasma concentration‐time curve (AUC0‐t and AUC0‐∞) was not altered by food intake immediately before oral dosing. Values of Cmax, Tmax, and AUC were comparable when telbivudine was administered under fed and fasting conditions. Results from this study indicated that the absorption of telbivudine was not affected by a high‐fat/high‐calorie meal; telbivudine can therefore be administered orally with no regard to the timing of meals.
Numbers
Authors: Weems Mary E.
Published: February 2006

The United States of America has had a long history of stigmatizing the issue of mental health. The current push in and outside social organizations to break the silence around mental health is beginning to make inroads toward positive social change, but we are a long way from conquering the negative stereotypes that adversely affect the lives of millions of people. This play was written in response to a lived experience during a walk through a cemetery for former residents of an asylum that used to exist on what are now Ohio University grounds.
Action Research Meets Critical Pedagogy
Authors: Miskovic Maya , Hoop Katrina
Published: February 2006

This article describes and critically examines the collaborative research process between an urban university’s research center and its community partners. The authors link the theoretical framework of collaborative research, participatory action research, and critical pedagogy to their personal experiences involving two collaborative research projects in which they participated. The projects were designed to foster engagement of youth in civic life through social research and to raise awareness of social inequality and injustice. The authors critically examine various phases of research with a particular focus on the following challenges: recruitment and attendance issues, development, language and methods issues, and the university and funding agency-driven push for a “product.” The authors point out the strengths and weaknesses of the collaborative approach and problematize issues not visible in the final research reports. Finally, strategies for enhancing the quality of the collaborative research involving youth are proposed.
Use of CD44 by CD4+ Th1 and Th2 lymphocytes to roll and adhere
Authors: Bonder Claudine S. , Clark Stephen R. , Norman M. Ursula , Johnson Pauline , Kubes Paul
Published: February 2006

Localization of circulating lymphocytes to a site of inflammation is paramount for the development and maintenance of an immune response. In vitro studies using cell lines have previously demonstrated that rolling and adhesion of lymphocytes on endothelium requires CD44 interactions with hyaluronan (HA). To date, whether CD44 has a role in mediating CD4+-polarized T-helper 1 (Th1) and Th2 lymphocyte interactions with the endothelium in vivo is yet to be determined. In this study we used intravital microscopy to demonstrate that both Th1 and Th2 lymphocytes use CD44 to roll and adhere to tumor necrosis factor-α (TNFα)–activated microvasculature. Furthermore, chimeric studies imply that CD44 expression by both the endothelium and lymphocytes is essential for these interactions to occur. HA was also necessary for T cell–endothelial cell interactions in vivo and Th1 and Th2 cells rolled on immobilized HA in vitro via CD44. In vitro, both Th1 and Th2 lymphocytes have increased expression of CD44 and greater binding of fluorescent HA than naive cells. The interactions of Th1 and Th2 cells were entirely dependent upon both P-selectin and CD44 in vivo, but did not appear to be counter ligands in vitro. Taken together, these results suggest that CD44 and HA are key to both Th1 and Th2 lymphocyte interactions with the TNFα-activated endothelium and raises the possibility of cooperativity between the P-selectin/PSGL-1 and HA/CD44 pathways for Th1 and Th2 rolling in vivo.
Eradication of minimal residual disease in hairy cell leukemia
Authors: Ravandi Farhad , Jorgensen Jeffrey L. , O'Brien Susan M. , Verstovsek Srdan , Koller Charles A. , Faderl Stefan , Giles Francis J. , Ferrajoli Alessandra , Wierda William G. , Odinga Shirley , Huang Xuelin , Thomas Deborah A. , Freireich Emil J. , Jones Dan , Keating Michael J. , Kantarjian Hagop M.
Published: February 2006

Although the nucleoside analogs cladribine and pentostatin produce high response rates in patients with hairy cell leukemia (HCL), a significant number of patients eventually relapse. Several studies have demonstrated that patients with complete remission (CR) have a longer disease-free survival. Therefore, strategies to improve on the initial response to nucleoside analog therapy are likely to be beneficial, at least for a proportion of patients. We have treated 13 patients with newly diagnosed HCL (n = 11) or after failure of one prior chemotherapy (n = 2) with cladribine (5.6 mg/m2 given intravenously over 2 hours daily for 5 days) followed by 8 weekly doses of rituximab (375 mg/m2). All patients achieved a CR and minimal residual disease (MRD) assessed by consensus primer polymerase chain reaction (PCR) or flow cytometry was eradicated in 11 (92%) of 12 and in 12 (92%) of 13 of patients, respectively. There was no decline in the absolute CD4 and CD8 lymphocyte number after rituximab. We conclude that eradication of MRD in HCL is possible. Whether this leads to a reduced risk of relapse would need to be evaluated in a larger number of patients and with longer follow-up. Disease characteristics may potentially be used to identify patients that are more likely to benefit from such additional therapy.
Biclustering of gene expression data by non-smooth non-negative matrix factorization
Authors: Carmona-Saez Pedro , Pascual-Marqui Roberto D , Tirado F , Carazo Jose M , Pascual-Montano Alberto
Published: February 2006

Background

The extended use of microarray technologies has enabled the generation and accumulation of gene expression datasets that contain expression levels of thousands of genes across tens or hundreds of different experimental conditions. One of the major challenges in the analysis of such datasets is to discover local structures composed by sets of genes that show coherent expression patterns across subsets of experimental conditions. These patterns may provide clues about the main biological processes associated to different physiological states.

Results

In this work we present a methodology able to cluster genes and conditions highly related in sub-portions of the data. Our approach is based on a new data mining technique, Non-smooth Non-Negative Matrix Factorization (n sNMF), able to identify localized patterns in large datasets. We assessed the potential of this methodology analyzing several synthetic datasets as well as two large and heterogeneous sets of gene expression profiles. In all cases the method was able to identify localized features related to sets of genes that show consistent expression patterns across subsets of experimental conditions. The uncovered structures showed a clear biological meaning in terms of relationships among functional annotations of genes and the phenotypes or physiological states of the associated conditions.

Conclusion

The proposed approach can be a useful tool to analyze large and heterogeneous gene expression datasets. The method is able to identify complex relationships among genes and conditions that are difficult to identify by standard clustering algorithms.
Integrating protein structures and precomputed genealogies in the Magnum database: Examples with cellular retinoid binding proteins
Authors: Bradley Michael E , Benner Steven A
Published: February 2006

Background

When accurate models for the divergent evolution of protein sequences are integrated with complementary biological information, such as folded protein structures, analyses of the combined data often lead to new hypotheses about molecular physiology. This represents an excellent example of how bioinformatics can be used to guide experimental research. However, progress in this direction has been slowed by the lack of a publicly available resource suitable for general use.

Results

The precomputed Magnum database offers a solution to this problem for ca. 1,800 full-length protein families with at least one crystal structure. The Magnum deliverables include 1) multiple sequence alignments, 2) mapping of alignment sites to crystal structure sites, 3) phylogenetic trees, 4) inferred ancestral sequences at internal tree nodes, and 5) amino acid replacements along tree branches. Comprehensive evaluations revealed that the automated procedures used to construct Magnum produced accurate models of how proteins divergently evolve, or genealogies, and correctly integrated these with the structural data. To demonstrate Magnum's capabilities, we asked for amino acid replacements requiring three nucleotide substitutions, located at internal protein structure sites, and occurring on short phylogenetic tree branches. In the cellular retinoid binding protein family a site that potentially modulates ligand binding affinity was discovered. Recruitment of cellular retinol binding protein to function as a lens crystallin in the diurnal gecko afforded another opportunity to showcase the predictive value of a browsable database containing branch replacement patterns integrated with protein structures.

Conclusion

We integrated two areas of protein science, evolution and structure, on a large scale and created a precomputed database, known as Magnum, which is the first freely available resource of its kind. Magnum provides evolutionary and structural bioinformatics resources that are useful for identifying experimentally testable hypotheses about the molecular basis of protein behaviors and functions, as illustrated with the examples from the cellular retinoid binding proteins.
Bias in error estimation when using cross-validation for model selection
Authors: Varma Sudhir , Simon Richard
Published: February 2006

Background

Cross-validation (CV) is an effective method for estimating the prediction error of a classifier. Some recent articles have proposed methods for optimizing classifiers by choosing classifier parameter values that minimize the CV error estimate. We have evaluated the validity of using the CV error estimate of the optimized classifier as an estimate of the true error expected on independent data.

Results

We used CV to optimize the classification parameters for two kinds of classifiers; Shrunken Centroids and Support Vector Machines (SVM). Random training datasets were created, with no difference in the distribution of the features between the two classes. Using these "null" datasets, we selected classifier parameter values that minimized the CV error estimate. 10-fold CV was used for Shrunken Centroids while Leave-One-Out-CV (LOOCV) was used for the SVM. Independent test data was created to estimate the true error. With "null" and "non null" (with differential expression between the classes) data, we also tested a nested CV procedure, where an inner CV loop is used to perform the tuning of the parameters while an outer CV is used to compute an estimate of the error.

The CV error estimate for the classifier with the optimal parameters was found to be a substantially biased estimate of the true error that the classifier would incur on independent data. Even though there is no real difference between the two classes for the "null" datasets, the CV error estimate for the Shrunken Centroid with the optimal parameters was less than 30% on 18.5% of simulated training data-sets. For SVM with optimal parameters the estimated error rate was less than 30% on 38% of "null" data-sets. Performance of the optimized classifiers on the independent test set was no better than chance.

The nested CV procedure reduces the bias considerably and gives an estimate of the error that is very close to that obtained on the independent testing set for both Shrunken Centroids and SVM classifiers for "null" and "non-null" data distributions.

Conclusion

We show that using CV to compute an error estimate for a classifier that has itself been tuned using CV gives a significantly biased estimate of the true error. Proper use of CV for estimating true error of a classifier developed using a well defined algorithm requires that all steps of the algorithm, including classifier parameter tuning, be repeated in each CV loop. A nested CV procedure provides an almost unbiased estimate of the true error.
Multiscale Hy3S: Hybrid stochastic simulation for supercomputers
Authors: Salis Howard , Sotiropoulos Vassilios , Kaznessis Yiannis N
Published: February 2006

Background

Stochastic simulation has become a useful tool to both study natural biological systems and design new synthetic ones. By capturing the intrinsic molecular fluctuations of "small" systems, these simulations produce a more accurate picture of single cell dynamics, including interesting phenomena missed by deterministic methods, such as noise-induced oscillations and transitions between stable states. However, the computational cost of the original stochastic simulation algorithm can be high, motivating the use of hybrid stochastic methods. Hybrid stochastic methods partition the system into multiple subsets and describe each subset as a different representation, such as a jump Markov, Poisson, continuous Markov, or deterministic process. By applying valid approximations and self-consistently merging disparate descriptions, a method can be considerably faster, while retaining accuracy. In this paper, we describe Hy3S, a collection of multiscale simulation programs.

Results

Building on our previous work on developing novel hybrid stochastic algorithms, we have created the Hy3S software package to enable scientists and engineers to both study and design extremely large well-mixed biological systems with many thousands of reactions and chemical species. We have added adaptive stochastic numerical integrators to permit the robust simulation of dynamically stiff biological systems. In addition, Hy3S has many useful features, including embarrassingly parallelized simulations with MPI; special discrete events, such as transcriptional and translation elongation and cell division; mid-simulation perturbations in both the number of molecules of species and reaction kinetic parameters; combinatorial variation of both initial conditions and kinetic parameters to enable sensitivity analysis; use of NetCDF optimized binary format to quickly read and write large datasets; and a simple graphical user interface, written in Matlab, to help users create biological systems and analyze data. We demonstrate the accuracy and efficiency of Hy3S with examples, including a large-scale system benchmark and a complex bistable biochemical network with positive feedback. The software itself is open-sourced under the GPL license and is modular, allowing users to modify it for their own purposes.

Conclusion

Hy3S is a powerful suite of simulation programs for simulating the stochastic dynamics of networks of biochemical reactions. Its first public version enables computational biologists to more efficiently investigate the dynamics of realistic biological systems.
Polymorphism discovery and association analyses of the interferon genes in type 1 diabetes
Authors: Morris Gerard AJ , Lowe Christopher E , Cooper Jason D , Payne Felicity , Vella Adrian , Godfrey Lisa , Hulme John S , Walker Neil M , Healy Barry C , Lam Alex C , Lyons Paul A , Todd John A
Published: February 2006

Background

The aetiology of the autoimmune disease type 1 diabetes (T1D) involves many genetic and environmental factors. Evidence suggests that innate immune responses, including the action of interferons, may also play a role in the initiation and/or pathogenic process of autoimmunity. In the present report, we have adopted a linkage disequilibrium (LD) mapping approach to test for an association between T1D and three regions encompassing 13 interferon alpha (IFNA) genes, interferon omega-1 (IFNW1), interferon beta-1 (IFNB1), interferon gamma (IFNG) and the interferon consensus-sequence binding protein 1 (ICSBP1).

Results

We identified 238 variants, most, single nucleotide polymorphisms (SNPs), by sequencing IFNA, IFNB1, IFNW1 and ICSBP1, 98 of which where novel when compared to dbSNP build 124. We used polymorphisms identified in the SeattleSNP database for INFG. A set of tag SNPs was selected for each of the interferon and interferon-related genes to test for an association between T1D and this complex gene family. A total of 45 tag SNPs were selected and genotyped in a collection of 472 multiplex families.

Conclusion

We have developed informative sets of SNPs for the interferon and interferon related genes. No statistical evidence of a major association between T1D and any of the interferon and interferon related genes tested was found.
Molecular targets for rapid identification of Brucella spp
Authors: Ratushna Vladyslava G , Sturgill David M , Ramamoorthy Sheela , Reichow Sherry A , He Yongqun , Lathigra Raju , Sriranganathan Nammalwar , Halling Shirley M , Boyle Stephen M , Gibas Cynthia J
Published: February 2006

Background

Brucella is an intracellular pathogen capable of infecting animals and humans. There are six recognized species of Brucella that differ in their host preference. The genomes of the three Brucella species have been recently sequenced. Comparison of the three revealed over 98% sequence similarity at the protein level and enabled computational identification of common and differentiating genes. We validated these computational predictions and examined the expression patterns of the putative unique and differentiating genes, using genomic and reverse transcription PCR. We then screened a set of differentiating genes against classical Brucella biovars and showed the applicability of these regions in the design of diagnostic tests.

Results

We have identified and tested set of molecular targets that are associated in unique patterns with each of the sequenced Brucella spp. A comprehensive comparison was made among the published genome sequences of B. abortus, B. melitensis and B. suis. The comparison confirmed published differences between the three Brucella genomes, and identified subsets of features that were predicted to be of interest in a functional comparison of B. melitensis and B. suis to B. abortus. Differentiating sequence regions from B. abortus, B. melitensis and B. suis were used to develop PCR primers to test for the existence and in vitro transcription of these genes in these species. Only B. suis is found to have a significant number of unique genes, but combinations of genes and regions that exist in only two out of three genomes and are therefore useful for diagnostics were identified and confirmed.

Conclusion

Although not all of the differentiating genes identified were transcribed under steady state conditions, a group of genes sufficient to discriminate unambiguously between B. suis, B. melitensis, and B. abortus was identified. We present an overview of these genomic differences and the use of these features to discriminate among a number of Brucella biovars.
Expression of hemagglutinin protein from the avian influenza virus H5N1 in a baculovirus/insect cell system significantly enhanced by suspension culture
Authors: Nwe Nitar , He Qigai , Damrongwatanapokin Sudarat , Du Qingyun , Manopo Ivanus , Limlamthong Yukol , Fenner Beau James , Spencer Lynn , Kwang Jimmy
Published: February 2006

Background

Prevention of a possible avian influenza pandemic necessitates the development of rapid diagnostic tests and the eventual production of a vaccine.

Results

For vaccine production, hemagglutinin (HA1) from avian influenza H5N1 was expressed from a recombinant baculovirus. Recombinant HA1 was expressed in monolayer or suspension culture insect cells by infection with the recombinant baculovirus. The yield of rHA1 from the suspension culture was 68 mg/l, compared to 6 mg/l from the monolayer culture. Immunization of guinea pigs with 50 μg of rHA1 yielded hemagglutinin inhibition and virus neutralization titers of 1:160 after two times vaccination with rHA1 protein.

Conclusion

Thus, the production of rHA1 using an insect suspension cell system provides a promising basis for economical production of a H5 antigen.
Use of flow cytometry for the adhesion analysis of Streptococcus pyogenes mutant strains to epithelial cells: investigation of the possible role of surface pullulanase and cysteine protease, and the transcriptional regulator Rgg
Authors: Hytönen Jukka , Haataja Sauli , Finne Jukka
Published: February 2006

Background

Flow cytometry based adherence assay is a potentially powerful but little used method in the study of bacterial binding to host structures. We have previously characterized a glycoprotein-binding activity in Streptococcus pyogenes called 'strepadhesin' binding to thyroglobulin, submaxillar mucin, fetuin and asialofetuin. We have identified surface-associated pullulanase (PulA) and cysteine protease (SpeB) as carriers of strepadhesin activity. In the present paper, we investigated the use of flow cytometry as a method to study the binding of Rgg, SpeB and PulA knock-out strains to cultured human epithelial cells.

Results

Streptococcal mutants were readily labelled with CFDA-SE and their binding to epithelial cells could be effectively studied by flow cytometry. A strain deficient in Rgg expression showed increased binding to the analyzed epithelial cell lines of various origin. Inactivation of SpeB had no effect on the adhesion, while PulA knock-out strains displayed decreased binding to the cell lines.

Conclusion

These results suggest that the flow cytometric assay is a valuable tool in the analysis of S. pyogenes adherence to host cells. It appears to be an efficient and sensitive tool for the characterization of interactions between the bacteria and the host at the molecular level. The results also suggest a role for Rgg regulated surface molecules, like PulA, in the adhesion of S. pyogenes to host cells.
Can electronic search engines optimize screening of search results in systematic reviews: an empirical study
Authors: Sampson Margaret , Barrowman Nicholas J , Moher David , Clifford Tammy J , Platt Robert W , Morrison Andra , Klassen Terry P , Zhang Li
Published: February 2006

Background

Most electronic search efforts directed at identifying primary studies for inclusion in systematic reviews rely on the optimal Boolean search features of search interfaces such as DIALOG® and Ovid™. Our objective is to test the ability of an Ultraseek® search engine to rank MEDLINE® records of the included studies of Cochrane reviews within the top half of all the records retrieved by the Boolean MEDLINE search used by the reviewers.

Methods

Collections were created using the MEDLINE bibliographic records of included and excluded studies listed in the review and all records retrieved by the MEDLINE search. Records were converted to individual HTML files. Collections of records were indexed and searched through a statistical search engine, Ultraseek, using review-specific search terms. Our data sources, systematic reviews published in the Cochrane library, were included if they reported using at least one phase of the Cochrane Highly Sensitive Search Strategy (HSSS), provided citations for both included and excluded studies and conducted a meta-analysis using a binary outcome measure. Reviews were selected if they yielded between 1000–6000 records when the MEDLINE search strategy was replicated.

Results

Nine Cochrane reviews were included. Included studies within the Cochrane reviews were found within the first 500 retrieved studies more often than would be expected by chance. Across all reviews, recall of included studies into the top 500 was 0.70. There was no statistically significant difference in ranking when comparing included studies with just the subset of excluded studies listed as excluded in the published review.

Conclusion

The relevance ranking provided by the search engine was better than expected by chance and shows promise for the preliminary evaluation of large results from Boolean searches. A statistical search engine does not appear to be able to make fine discriminations concerning the relevance of bibliographic records that have been pre-screened by systematic reviewers.
Q fever endocarditis masquerading as Mixed cryoglobulinemia type II. A case report and review of the literature
Authors: Rafailidis Petros I , Dourakis Spiros P , Fourlas Christos A
Published: February 2006

Background

The clinical manifestations of Q fever endocarditis are protean in nature. Mixed cryoglobulinemia type II is rarely a facet of the presenting clinical manifestations of Q fever endocarditis.

Case presentation

We report a case of a 65-year-old pensioner with such an association and review the literature. As transesophageal echocardiograms are usually normal and blood cultures are usually negative in Q fever endocarditis, many of the manifestations (fever, rash, glomerulonephritis/evidence of renal disease, low serum C4 complement component, presence of mixed type II cryoglobulin, constitutional symptoms as arthralgias and fatigue) can be attributed to Mixed cryoglobulinemia type II per se. The use of Classic Duke Endocarditis Service criteria does not always suffice for the diagnosis of Q fever.

Conclusion

The application of the modified criteria proposed by Fournier et al for the improvement of the diagnosis of Q fever endocarditis will help to reach the diagnosis earlier and thus reduce the high mortality of the disease. We would like to stress the importance of ruling out the diagnosis of Q fever endocarditis in cases of mixed type II cryoglobulinemia.
Leptin and leptin receptor polymorphisms are associated with increased risk and poor prognosis of breast carcinoma
Authors: Snoussi Kaouther , Strosberg A Donny , Bouaouina Noureddine , Ahmed Slim Ben , Helal A Noureddine , Chouchane Lotfi
Published: February 2006

Background

Leptin (LEP) has been consistently associated with angiogenesis and tumor growth. Leptin exerts its physiological action through its specific receptor (LEPR). We have investigated whether genetic variations in
LEP
and
LEPR
have implications for susceptibility to and prognosis in breast carcinoma.

Methods

We used the polymerase chain reaction and restriction enzyme digestion to characterize the variation of the
LEP
and
LEPR
genes in 308 unrelated Tunisian patients with breast carcinoma and 222 healthy control subjects. Associations of the clinicopathologic parameters and these genetic markers with the rates of the breast carcinoma-specific overall survival (OVS) and the disease free survival (DFS) were assessed using univariate and multivariate analyses.

Results

A significantly increased risk of breast carcinoma was associated with heterozygous
LEP (-2548) GA
(OR = 1.45; P = 0.04) and homozygous
LEP (-2548) AA
(OR = 3.17; P = 0.001) variants. A highly significant association was found between the heterozygous
LEPR 223QR
genotype (OR = 1.68; P = 0.007) or homozygous
LEPR 223RR
genotype (OR = 2.26; P = 0.001) and breast carcinoma.

Moreover, the presence of the
LEP (-2548) A
allele showed a significant association with decreased disease-free survival in breast carcinoma patients, and the presence of the
LEPR 223R
allele showed a significant association with decreased overall survival.

Conclusion

Our results indicated that the polymorphisms in
LEP
and
LEPR
genes are associated with increased breast cancer risk as well as disease progress, supporting our hypothesis for leptin involvement in cancer pathogenesis.
A reference frame for blood volume in children and adolescents
Authors: Raes Ann , Van Aken Sarah , Craen Margarita , Donckerwolcke Raymond , Walle Johan Vande
Published: February 2006

Background

Our primary purpose was to determine the normal range and variability of blood volume (BV) in healthy children, in order to provide reference values during childhood and adolescence. Our secondary aim was to correlate these vascular volumes to body size parameters and pubertal stages, in order to determine the best normalisation parameter.

Methods

Plasma volume (PV) and red cell volume (RCV) were measured and F-cell ratio was calculated in 77 children with idiopathic nephrotic syndrome in drug-free remission (mean age, 9.8 ± 4.6 y). BV was calculated as the sum of PV and RCV. Due to the dependence of these values on age, size and sex, all data were normalised for body size parameters.

Results

BV normalised for lean body mass (LBM) did not differ significantly by sex (p < 0.376) or pubertal stage (p < 0.180), in contrast to normalisation for the other anthropometric parameters. There was no significant difference between reference values for children and adults.

Conclusion

LBM was the anthropometric index most closely correlated to vascular fluid volumes, independent of age, gender and pubertal stage.
Screening for antimicrobial activity of ten medicinal plants used in Colombian folkloric medicine: A possible alternative in the treatment of non-nosocomial infections
Authors: Rojas Jhon J , Ochoa Veronica J , Ocampo Saul A , Muñoz John F
Published: February 2006

Background

The antimicrobial activity and Minimal Inhibitory Concentration (MIC) of the extracts of Bidens pilosa L., Bixa orellana L., Cecropia peltata L., Cinchona officinalis L., Gliricidia sepium H.B. & K, Jacaranda mimosifolia D.Don, Justicia secunda Vahl., Piper pulchrum C.DC, P. paniculata L. and Spilanthes americana Hieron were evaluated against five bacteria (Staphylococcus aureus, Streptococcus β hemolític, Bacillus cereus, Pseudomonas aeruginosa, and Escherichia coli), and one yeast (Candida albicans). These plants are used in Colombian folk medicine to treat infections of microbial origin.

Methods

Plants were collected by farmers and traditional healers. The ethanol, hexane and water extracts were obtained by standard methods. The antimicrobial activity was found by using a modified agar well diffusion method. All microorganisms were obtained from the American Type Culture Collection (ATCC). MIC was determined in the plant extracts that showed some efficacy against the tested microorganisms. Gentamycin sulfate (1.0 μg/ml), clindamycin (0.3 μg/ml) and nystatin (1.0 μg/ml) were used as positive controls.

Results

The water extracts of Bidens pilosa L., Jacaranda mimosifolia D.Don, and Piper pulchrum C.DC showed a higher activity against Bacillus cereus and Escherichia coli than gentamycin sulfate. Similarly, the ethanol extracts of all species were active against Staphylococcus aureus except for Justicia secunda. Furthermore, Bixa orellana L, Justicia secunda Vahl. and Piper pulchrum C.DC presented the lowest MICs against Escherichia coli (0.8, 0.6 and 0.6 μg/ml, respectively) compared to gentamycin sulfate (0.9 8g/ml). Likewise, Justicia secunda and Piper pulchrum C.DC showed an analogous MIC against Candida albicans (0.5 and 0.6 μg/ml, respectively) compared to nystatin (0.6 μg/ml). Bixa orellana L, exhibited a better MIC against Bacillus cereus (0.2 μg/ml) than gentamycin sulfate (0.5 μg/ml).

Conclusion

This in vitro study corroborated the antimicrobial activity of the selected plants used in folkloric medicine. All these plants were effective against three or more of the pathogenic microorganisms. However, they were ineffective against Streptococcus β hemolytic and Pseudomonas aeruginosa. Their medicinal use in infections associated with these two species is not recommended. This study also showed that Bixa orellana L, Justicia secunda Vahl. and Piper pulchrum C.DC could be potential sources of new antimicrobial agents.
Selection of optimal recording sites for limited lead body surface potential mapping: A sequential selection based approach
Authors: Finlay Dewar D , Nugent Chris D , Donnelly Mark P , Lux Robert L , McCullagh Paul J , Black Norman D
Published: February 2006

Background

In this study we propose the development of a new algorithm for selecting optimal recording sites for limited lead body surface potential mapping. The proposed algorithm differs from previously reported methods in that it is based upon a simple and intuitive data driven technique that does not make any presumptions about deterministic characteristics of the data. It uses a forward selection based search technique to find the best combination of electrocardiographic leads.

Methods

The study was conducted using a dataset consisting of body surface potential maps (BSPM) recorded from 116 subjects which included 59 normals and 57 subjects exhibiting evidence of old Myocardial Infarction (MI). The performance of the algorithm was evaluated using spatial RMS voltage error and correlation coefficient to compare original and reconstructed map frames.

Results

In all, three configurations of the algorithm were evaluated and it was concluded that there was little difference in the performance of the various configurations. In addition to observing the performance of the selection algorithm, several lead subsets of 32 electrodes as chosen by the various configurations of the algorithm were evaluated. The rationale for choosing this number of recording sites was to allow comparison with a previous study that used a different algorithm, where 32 leads were deemed to provide an acceptable level of reconstruction performance.

Conclusion

It was observed that although the lead configurations suggested in this study were not identical to that suggested in the previous work, the systems did bear similar characteristics in that recording sites were chosen with greatest density in the precordial region.
Type-2 diabetes-induced changes in vascular extracellular matrix gene expression: Relation to vessel size
Authors: Song WeiWei , Ergul Adviye
Published: February 2006

Background

Hyperglycemia-induced changes in vascular wall structure contribute to the pathogenesis of diabetic microvascular and macrovascular complications. Matrix metalloproteinases (MMP), a family of proteolytic enzymes that degrade extracellular matrix (ECM) proteins, are essential for vascular remodeling. We have shown that endothelin-1 (ET-1) mediates increased MMP activity and associated vascular remodeling in Type 2 diabetes. However, the effect of Type 2 diabetes and/or ET-1 on the regulation of ECM and MMP gene expression in different vascular beds remains unknown.

Methods

Aorta and mesenteric artery samples were isolated from control, Type 2 diabetic Goto-Kakizaki (GK) rats and GK rats treated with ETA antagonist ABT-627. Gene expression profile of MMP-2, MMP-9, MT1-MMP, fibronectin, procollagen type 1, c-fos and c-jun, were determined by quantitative real-time (qRT) PCR. In addition, aortic gene expression profile was evaluated by an ECM & Adhesion Molecules pathway specific microarray approach.

Results

Analysis of the qRT-PCR data demonstrated a significant increase in mRNA levels of MMPs and ECM proteins as compared to control animals after 6 weeks of mild diabetes. Futhermore, these changes were comparable in aorta and mesentery samples. In contrast, treatment with ETA antagonist prevented diabetes-induced changes in expression of MMPs and procollagen type 1 in mesenteric arteries but not in aorta. Microaarray analysis provided evidence that 27 extracellular matrix genes were differentially regulated in diabetes. Further qRT-PCR with selected 7 genes confirmed the microarray data.

Conclusion

These results suggest that the expression of both matrix scaffold protein and matrix degrading MMP genes are altered in macro and microvascular beds in Type 2 diabetes. ETA antagonism restores the changes in gene expression in the mesenteric bed but not in aorta suggesting that ET-1 differentially regulates microvascular gene expression in Type 2 diabetes.