bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cytometric detection of antigen-specific IFN-γ/IL-2 secreting cells in the diagnosis of tuberculosis
Authors: Sargentini Valeria , Mariotti Sabrina , Carrara Stefania , Gagliardi Maria Cristina , Teloni Raffaela , Goletti Delia , Nisini Roberto 
Published: June 2009

AbstractBackgroundThe purpose of this study was to further characterize the immune response toMycobacterium tuberculosis(Mtb) antigens, in order to provide new insight into host-pathogen interactions in tuberculosis (TB), and to offer tools for a more accurate diagnosis of the different stages of TB.MethodsT-cell responses to Bacillus Calmette-Guérin (BCG), purified protein derivative (PPD), early secretory antigenic target-6 (ESAT-6) protein and culture filtrate protein-10 kDa (CFP-10) were measured in terms of interferon (IFN)-γ and interleukin (IL)-2 release, using a novel flow cytometric cell-secreting cytokine detection technique. The study was conducted on peripheral blood mononuclear cells (PBMC) obtained from active TB patients, latently TB infected individuals, and healthy donors. IL-10 and IL-17 were also measured to test their possible role as indicators of disease activity.ResultsWe confirmed that the enumeration of IFN-γ releasing cells upon Mtb-specific stimulation is sufficient to identify TB patients and that CD8+ T cells concur to IFN-γ secretion. IL-2 secreting cells were more frequently observed in latent TB infected individuals compared to active TB patients, suggesting that measurement of cells secreting this cytokine could be a marker of disease stage. No discriminating role was associated to IL-10 and IL-17 release in TB patients.ConclusionOur data indicate that the flow cytometric cytokine-secreting cell detection technique may be envisaged as an additional tool for TB diagnosis allowing the analysis of the immune response toM. tuberculosis-related antigens in the different stages of TB.
Type-1 Collagen differentially alters β-catenin accumulation in primary Dupuytren's Disease cord and adjacent palmar fascia cells
Authors: Vi Linda , Njarlangattil Anna , Wu Yan , Gan Bing Siang , O'Gorman David B 
Published: June 2009

Abstract

Background
Dupuytren's Disease (DD) is a debilitating contractile fibrosis of the palmar fascia characterised by excess collagen deposition, contractile myofibroblast development, increased Transforming Growth Factor-β levels and β-catenin accumulation. The aim of this study was to determine if a collagen-enriched environment, similar to in vivo conditions, altered β-catenin accumulation by primary DD cells in the presence or absence of Transforming Growth Factor-β.

Methods
Primary DD and patient matched, phenotypically normal palmar fascia (PF) cells were cultured in the presence or absence of type-1 collagen and Transforming Growth Factor-β1. β-catenin and α-smooth muscle actin levels were assessed by western immunoblotting and immunofluorescence microscopy.

Results
DD cells display a rapid depletion of cellular β-catenin not evident in patient-matched PF cells. This effect was not evident in either cell type when cultured in the absence of type-1 collagen. Exogenous addition of Transforming Growth Factor-β1 to DD cells in collagen culture negates the loss of β-catenin accumulation. Transforming Growth Factor-β1-induced α-smooth muscle actin, a marker of myofibroblast differentiation, is attenuated by the inclusion of type-1 collagen in cultures of DD and PF cells.

Conclusion
Our findings implicate type-1 collagen as a previously unrecognized regulator of β-catenin accumulation and a modifier of TGF-β1 signaling specifically in primary DD cells. These data have implications for current treatment modalities as well as the design of in vitro models for research into the molecular mechanisms of DD.
Modelling substrate specificity and enantioselectivity for lipases and esterases by substrate-imprinted docking
Authors: Juhl P Benjamin , Trodler Peter , Tyagi Sadhna , Pleiss Jürgen 
Published: June 2009

Abstract

Background
Previously, ways to adapt docking programs that were developed for modelling inhibitor-receptor interaction have been explored. Two main issues were discussed. First, when trying to model catalysis a reaction intermediate of the substrate is expected to provide more valid information than the ground state of the substrate. Second, the incorporation of protein flexibility is essential for reliable predictions.

Results
Here we present a predictive and robust method to model substrate specificity and enantioselectivity of lipases and esterases that uses reaction intermediates and incorporates protein flexibility. Substrate-imprinted docking starts with covalent docking of reaction intermediates, followed by geometry optimisation of the resulting enzyme-substrate complex. After a second round of docking the same substrate into the geometry-optimised structures, productive poses are identified by geometric filter criteria and ranked by their docking scores. Substrate-imprinted docking was applied in order to model (i) enantioselectivity of
Candida antarctica
lipase B and a W104A mutant, (ii) enantioselectivity and substrate specificity of
Candida rugosa
lipase and
Burkholderia cepacia
lipase, and (iii) substrate specificity of an acetyl- and a butyrylcholine esterase toward the substrates acetyl- and butyrylcholine.

Conclusion
The experimentally observed differences in selectivity and specificity of the enzymes were reproduced with an accuracy of 81%. The method was robust toward small differences in initial structures (different crystallisation conditions or a co-crystallised ligand), although large displacements of catalytic residues often resulted in substrate poses that did not pass the geometric filter criteria.
A case for using grid architecture for state public health informatics: the Utah perspective
Authors: Staes Catherine J , Xu Wu , LeFevre Samuel D , Price Ronald C , Narus Scott P , Gundlapalli Adi , Rolfs Robert , Nangle Barry , Samore Matthew , Facelli Julio C 
Published: June 2009

Abstract
This paper presents the rationale for designing and implementing the next-generation of public health information systems using grid computing concepts and tools. Our attempt is to evaluate all grid types including data grids for sharing information and computational grids for accessing computational resources on demand. Public health is a broad domain that requires coordinated uses of disparate and heterogeneous information systems. System interoperability in public health is limited. The next-generation public health information systems must overcome barriers to integration and interoperability, leverage advances in information technology, address emerging requirements, and meet the needs of all stakeholders. Grid-based architecture provides one potential technical solution that deserves serious consideration. Within this context, we describe three discrete public health information system problems and the process by which the Utah Department of Health (UDOH) and the Department of Biomedical Informatics at the University of Utah in the United States has approached the exploration for eventual deployment of a Utah Public Health Informatics Grid. These three problems are: i) integration of internal and external data sources with analytic tools and computational resources; ii) provide external stakeholders with access to public health data and services; and, iii) access, integrate, and analyze internal data for the timely monitoring of population health status and health services. After one year of experience, we have successfully implemented federated queries across disparate administrative domains, and have identified challenges and potential solutions concerning the selection of candidate analytic grid services, data sharing concerns, security models, and strategies for reducing expertise required at a public health agency to implement a public health grid.
Losartan counteracts the hyper-reactivity to angiotensin II and ROCK1 over-activation in aortas isolated from streptozotocin-injected diabetic rats
Authors: Failli Paola , Alfarano Chiara , Franchi-Micheli Sergio , Mannucci Edoardo , Cerbai Elisabetta , Mugelli Alessandro , Raimondi Laura 
Published: June 2009

AbstractBackgroundIn streptozotocin-injected rats (STZ-rats), we previously demonstrated a role for angiotensin II (AT-II) in cardiac remodelling and insulin resistance partially counteracted byin vivotreatment with losartan, an AT-II receptor antagonist.We now aimed to investigate the effect of treating diabetic STZ-rats with losartan on diabetes vascular response to vasoconstrictors.MethodsMale Wistar rats were randomly divided in four groups, two of them were assigned to receive losartan in the drinking water (20 mg/kg/day) until the experiment ending (3 weeks afterward). After 1 week, two groups, one of which receiving losartan, were injected in the tail vein with citrate buffer (normoglycemic, N and normoglycemic, losartan-treated, NL). The remaining received a single injection of streptozotocin (50 mg/kg in citrate i.v.) thus becoming diabetic (D) and diabetic losartan-treated (DL). Plasma glycaemia and blood pressure were measured in all animals before the sacrifice (15 days after diabetes induction).In aortic strips isolated from N, NL, D and DL rats we evaluated i) the isometric concentration-dependent contractile response to phenylephrine (Phe) and to AT-II; ii) the RhoA-kinase (ROCK1) activity and expression by enzyme-immunoassay and Western blot respectively.Key resultsThe concentration-dependent contractile effect of Phe was similar in aortas from all groups, whereas at all concentrations tested, AT-II contraction efficacy was 2 and half and 1 and half times higher in D and DL respectively in comparison with N and NL. AT-II contracture was similarly reduced in all groups by AT-II receptor antagonists, irbesartan or irbesartan plus PD123319. HA-1077 (10 μM), an inhibitor of ROCK1 activity, reduced AT-II efficacy (Δmg/mg tissue w.w.) by -3.5 ± 1.0, -4.6 ± 1.9, -22.1 ± 2.2 and -11.4 ± 1.3 in N, NL, D and DL respectively). ROCK1 activity and expression were higher in D than in N/NL and DL aortas.Conclusion and implicationsAortas isolated from STZ-rats present hyper-contracture to AT-II mainly dependent on the up-regulation of ROCK1 expression/activity. In vivo losartan treatment partially corrects AT-II hyper-contracture, limiting the increase in ROCK1 expression/activity. These data offer a new molecular mechanism supporting the rationale for using losartan in the prevention of diabetic vascular complications.
Combined effects of obesity and type 2 diabetes contribute to increased breast cancer risk in premenopausal women
Authors: Alokail Majed S , Al-Daghri Nasser M , Al-Attas Omar S , Hussain Tajamul 
Published: June 2009

AbstractBackgroundBoth obesity and type 2 diabetes are among the risk factors for breast cancer development. Combined effect of these metabolic abnormalities on breast cancer risk however, has not been examined in premenopausal women. We tested this association in type 2 diabetic women, categorized as obese, overweight and normal body weight groups based on BMI.Design and methodsA total of 101 subjects were included in this study. Serum levels of IL-6, TNF-α, C reactive protein, leptin, TGF-α, adiponectin and insulin were measured by ELISA. Data were logarithmically transformed for variables not normally distributed. Analysis of variance with post-hoc Bonferroni was applied to compare the data between the groups. Simple and partial correlation coefficients between the variables were determined and a stepwise multiple linear regression analysis was performed to determine the relationships between the variables of interest.ResultsSignificantly increased levels of IL-6, C reactive protein, leptin and significantly decreased levels of adiponectin were found in obese group, while the levels of TNF-α and TGF-α were unaltered. A positive correlation between waist circumference and IL-6 was found in obese group. Similarly, C reactive protein, waist and hip circumferences were linearly correlated with BMI in obese group. Stepwise multiple linear regression analysis revealed several significant predictors for breast cancer risk.ConclusionObesity and type 2 diabetes, owing to their effects on adipocytokines and inflammatory mediators, contribute to increased breast cancer risk in premenopausal women. This study emphasizes healthy life style and better management of these metabolic disorders to avoid the pathogenesis of breast cancer and of other chronic diseases.
Marked differences in CRP genotype frequencies between the Fulani and sympatric ethnic groups in Africa
Authors: Israelsson Elisabeth , Ekström Mattias , Nasr Amre , Dolo Amagana , Kearsley Susannah , Arambepola Gishanthi , Homann Manijeh Vafa , Maiga Bakary , Doumbo Ogobara K , ElGhazali Gehad , Giha Hayder A , Troye-Blomberg Marita , Berzins Klavs , Tornvall Per 
Published: June 2009

AbstractBackgroundC-reactive protein (CRP) is an acute phase protein that can activate various immune cells and bind to certain Fcγ receptors. The latter may compete with the binding of IgG antibodies to these receptors and could thereby interfere with the antigen-specific immune response. Polymorphisms in the promoter region of theCRPgene have been strongly associated with the plasma concentration of CRP. The known lower susceptibility to malaria in the Fulani ethnic group, as compared to their sympatric neighbours in Africa, has been linked to different genetic backgrounds. The present study was performed to investigate if polymorphisms in the CRP gene could contribute to the lower susceptibility to malaria seen in the Fulani ethnic group.MethodsThe CRP -717 T>C, -286 C>T>A, and +1444 C>T polymorphisms were analysed in asymptomatic Fulani and non-Fulani individuals from Mali and Sudan using Pyrosequencing T and TaqMan r MGB probes.ResultsThe rare -286 A allele, previously shown to be associated with increased CRP expression and plasma levels, was shown to be more frequent in the non-Fulani ethnic groups as compared to the sympatric Fulani ethnic group both in Mali and Sudan. The common -717 T allele was more prevalent in the non-Fulani ethnic group compared to the sympatric Fulani ethnic group, but only in Mali. The parasite prevalence was increased for the -286 A allele, but not for the -717 T allele. No differences regarding genotype frequency or parasite prevalence were seen for +1444 C>T.ConclusionThis study indicate that CRP may play an important role in the immune responses to malaria, and that the -286 C/T/A CRP polymorphism may be a contributing factor to the lower susceptibility to malaria seen in the Fulani.
Analysis of von Willebrand factor A domain-related protein (WARP) polymorphism in temperate and tropical Plasmodium vivax field isolates
Authors: Gholizadeh Saber , Djadid Navid Dinparast , Basseri Hamid Reza , Zakeri Sedigheh , Ladoni Hossein 
Published: June 2009

AbstractBackgroundThe identification of key molecules is crucial for designing transmission-blocking vaccines (TBVs), among those ookinete micronemal proteins are candidate as a general class of malaria transmission-blocking targets. Here, the sequence analysis of an extra-cellular malaria protein expressed in ookinetes, named von Willebrand factor A domain-related protein (WARP), is reported in 91Plasmodium vivaxisolates circulating in different regions of Iran.MethodsClinical isolates were collected from north temperate and southern tropical regions in Iran. Primers have been designed based onP. vivaxsequence (ctg_6991) which amplified a fragment of about 1044 bp with no size variation. Direct sequencing of PCR products was used to determine polymorphism and further bioinformatics analysis inP. vivaxsexual stage antigen,pvwarp.ResultsAmplifiedpvwarpgene showed 886 bp in size, with no intron. BLAST analysis showed a similarity of 98–100% toP. vivaxSal-I strain; however, Iranian isolates had 2 bp mismatches in 247 and 531 positions that were non-synonymous substitution [T (ACT) to A (GCT) and R (AGA) to S (AGT)] in comparison with the Sal-I sequence.ConclusionThis study presents the first large-scale survey onpvwarppolymorphism in the world, which provides baseline data for developing WARP-based TBV against both temperate and tropicalP. vivaxisolates.
Tolerance of a standard intact protein formula versus a partially hydrolyzed formula in healthy, term infants
Authors: Berseth Carol Lynn , Mitmesser Susan Hazels , Ziegler Ekhard E , Marunycz John D , Vanderhoof Jon 
Published: June 2009

Abstract

Background
Parents who perceive common infant behaviors as formula intolerance-related often switch formulas without consulting a health professional. Up to one-half of formula-fed infants experience a formula change during the first six months of life.

Methods
The objective of this study was to assess discontinuance due to study physician-assessed formula intolerance in healthy, term infants. Infants (335) were randomized to receive either a standard intact cow milk protein formula (INTACT) or a partially hydrolyzed cow milk protein formula (PH) in a 60 day non-inferiority trial. Discontinuance due to study physician-assessed formula intolerance was the primary outcome. Secondary outcomes included number of infants who discontinued for any reason, including parent-assessed.

Results
Formula intolerance between groups (INTACT, 12.3% vs. PH, 13.7%) was similar for infants who completed the study or discontinued due to study physician-assessed formula intolerance. Overall study discontinuance based on parent- vs. study physician-assessed intolerance for all infants (14.4 vs.11.1%) was significantly different (P = 0.001).

Conclusion
This study demonstrated no difference in infant tolerance of intact vs. partially hydrolyzed cow milk protein formulas for healthy, term infants over a 60-day feeding trial, suggesting nonstandard partially hydrolyzed formulas are not necessary as a first-choice for healthy infants. Parents frequently perceived infant behavior as formula intolerance, paralleling previous reports of unnecessary formula changes.

Trial Registration
clinicaltrials.gov: NCT00666120
Influence of conjugated linoleic acid on the porcine immune response and morbidity: a randomized controlled trial
Authors: Malovrh Tomaz , Kompan Lidija , Juntes Polona , Wraber Branka , Spindler-Vesel Alenka , Kompan Drago 
Published: June 2009

Abstract

Background
Conjugated linoleic acid (CLA) has diverse influences on the immune response in different experimental models. In the present study we investigated the effect of CLA feeding on inflammatory and immune responses in a piglet model. We studied the duration of this effect and possible detrimental effects of CLA feeding. After 12 weeks of CLA and control supplementation and washout, animals were sacrificed and parenchymal organs were histologically examined.

Results
In activated peripheral mononuclear cells interferon-γ was significantly (p = 0.008) lower in the CLA group by the end of the feeding period. This effect disappeared as soon as supplementation was stopped. No differences were found in the tumour necrosis factor-α, interleukin-10 production, serum immunoglobulin-G levels and fat infiltration of the liver, except that fat storage cell infiltration was significantly (p < 0.04) higher in the CLA-fed group. The effect of time for interferon-γ, interleukin-10 and immunoglobulin-G levels was statistically significant.

Conclusion
At the end of the feeding period the interferon-γ response was depressed. However, the maturation of the piglet immune system in our young pig model probably outweighs the impact of CLA feeding on the immune response, even though liver fat storage cell infiltration, which plays an important role in liver regeneration, increased during CLA feeding of the piglets.
Anti-tumor activity of patient-derived NK cells after cell-based immunotherapy – a case report
Authors: Milani Valeria , Stangl Stefan , Issels Rolf , Gehrmann Mathias , Wagner Beate , Hube Kathrin , Mayr Doris , Hiddemann Wolfgang , Molls Michael , Multhoff Gabriele 
Published: June 2009

AbstractBackgroundMembrane-bound heat shock protein 70 (Hsp70) serves as a tumor-specific recognition structure for Hsp70-peptide (TKD) plus IL-2 activated NK cells. A phase I clinical trial has shown that repeated re-infusions ofex vivoTKD/IL-2-activated, autologous leukapheresis product is safe. This study investigated the maintenance of the cytolytic activity of NK cells against K562 cells and autologous tumor after 6 plus 3 infusions of TKD/IL-2-activated effector cells.MethodsA stable tumor cell line was generated from the resected anastomotic relapse of a patient with colon carcinoma (pT3, N2, M0, G2). Two months after surgery, the patient received the first monthly i.v. infusion of hisex vivoTKD/IL-2-activated peripheral blood mononuclear cells (PBMNC). After 6 infusions and a pause of 3 months, the patient received another 3 cell infusions. The phenotypic characteristics and activation status of tumor and effector cells were determined immediately before and at times after each infusion.ResultsThe NK cell ligands Hsp70, MICA/B, and ULBP-1,2,3 were expressed on the patient's anastomotic relapse. An increased density of activatory NK cell receptors followingex vivostimulation correlated with an enhanced anti-tumoricidal activity. After 4 re-infusion cycles, the intrinsic cytolytic activity of non-stimulated PBMNC was significantly elevated and this heightened responsiveness persisted for up to 3 months after the last infusion. Another 2 re-stimulations with TKD/IL-2 restored the cytolytic activity after the therapeutic pause.ConclusionIn a patient with colon carcinoma, repeated infusions ofex vivoTKD/IL-2-activated PBMNC initiate an intrinsic NK cell-mediated cytolytic activity against autologous tumor cells.
AP-2α regulates migration of GN-11 neurons via a specific genetic programme involving the Axl receptor tyrosine kinase
Authors: Orso Francesca , Jäger Richard , Calogero Raffaele Adolfo , Schorle Hubert , Sismondi Piero , De Bortoli Michele , Taverna Daniela 
Published: June 2009

Abstract

Background

Neuronal migration is a crucial process that allows neurons to reach their correct target location to allow the nervous system to function properly. AP-2α is a transcription factor essential for neural crest cell migration and its mutation results in apoptosis within this cell population, as demonstrated by genetic models.

Results

We down-modulated AP-2α expression in GN-11 neurons by RNA interference and observe reduced neuron migration following the activation of a specific genetic programme including the Adhesion Related Kinase (Axl) gene. We prove that Axl is able to coordinate migration per se and by ChIP and promoter analysis we observe that its transcription is directly driven by AP-2α via the binding to one or more functional AP-2α binding sites present in its regulatory region. Analysis of migration in AP-2α null mouse embryo fibroblasts also reveals an essential role for AP-2α in cell movement via the activation of a distinct genetic programme.

Conclusion

We show that AP-2α plays an essential role in cell movement via the activation of cell-specific genetic programmes. Moreover, we demonstrate that the AP-2α regulated gene Axl is an essential player in GN-11 neuron migration.