bluuebunny/crossref_metadata_2025_split huggingface dataset:
Indoleamine 2,3-dioxygenase–expressing mature human monocyte-derived dendritic cells expand potent autologous regulatory T cells
Authors: Chung David J. , Rossi Marco , Romano Emanuela , Ghith Jennifer , Yuan Jianda , Munn David H. , Young James W. 
Published: May 2009

Abstract
A comprehensive understanding of the complex, autologous cellular interactions and regulatory mechanisms that occur during normal dendritic cell (DC)–stimulated immune responses is critical to optimizing DC-based immunotherapy. We have found that mature, immunogenic human monocyte-derived DCs (moDCs) up-regulate the immune-inhibitory enzyme, indoleamine 2,3-dioxygenase (IDO). Under stringent autologous culture conditions without exogenous cytokines, mature moDCs expand regulatory T cells (Tregs) by an IDO-dependent mechanism. The priming of resting T cells with autologous, IDO-expressing, mature moDCs results in up to 10-fold expansion of CD4+CD25brightFoxp3+CD127neg Tregs. Treg expansion requires moDC contact, CD80/CD86 ligation, and endogenous interleukin-2. Cytofluorographically sorted CD4+ CD25brightFoxp3+ Tregs inhibit as much as 80% to 90% of DC-stimulated autologous and allogeneic T-cell proliferation, in a dose-dependent manner at Treg:T-cell ratios of 1:1, 1:5, and as low as 1:25. CD4+CD25brightFoxp3+ Tregs also suppress the generation of cytotoxic T lymphocytes specific for the Wilms tumor antigen 1, resulting in more than an 80% decrease in specific target cell lysis. Suppression by Tregs is both contact-dependent and transforming growth factor-β–mediated. Although mature moDCs can generate Tregs by this IDO-dependent mechanism to limit otherwise unrestrained immune responses, inhibition of this counter-regulatory pathway should also prove useful in sustaining responses stimulated by DC-based immunotherapy.
CC chemokine ligand 2 down-modulation by selected Toll-like receptor agonist combinations contributes to T helper 1 polarization in human dendritic cells
Authors: Del Cornò Manuela , Michienzi Alessandro , Masotti Andrea , Da Sacco Letizia , Bottazzo Gian Franco , Belardelli Filippo , Gessani Sandra 
Published: May 2009

AbstractToll-like receptor (TLR) signaling activation by pathogens is critical to the induction of immune responses, and demands tight regulation. We describe in this study that CC chemokine ligand 2 (CCL2) secretion triggered by TLR4 or TLR8 engagement is strongly inhibited upon simultaneous activation of both TLRs in human monocyte-derived dendritic cells (DCs). Impaired CCL2 secretion occurs concomitantly to interleukin-12 up-regulation, being part of a complex regulatory circuit ensuring optimal T helper type 1 polarization. Interestingly, triggering selected TLRs or their combinations differently affects nuclear factor-κB p65 activation and microRNA expression. Overall, these results indicate that CCL2 supplies an important immunomodulatory role to DCs, and may contribute to dictate the cytokine profile in T helper type 1 responses induced by DCs.
HBV replication is significantly reduced by IL-6
Authors: Kuo Tzer-Min , Hu Cheng-po , Chen Ya-Ling , Hong Ming-Hsiang , Jeng King-Song , Liang Chun-Chin T , Chen Mong-Liang , Chang Chungming 
Published: May 2009

Abstract
Interleukin-6 (IL-6) is a pleiotropic cytokine with pivotal functions in the regulation of the biological responses of several target cells including hepatocytes. The level of serum IL-6 has been reported to be elevated in patients with chronic hepatitis B, cirrhosis and hepatocellular carcinoma and represents the best marker of HBV-related clinical progression as compared with several other cytokines. In this study, we found that IL-6 was able to effectively suppress hepatitis B virus (HBV) replication and prevent the accumulation of HBV covalently closed circular DNA (cccDNA) in a human hepatoma cell line. We also demonstrated that the suppression of HBV replication by IL-6 requires concurrently a moderate reduction of viral transcripts/core proteins and a marked decrease in viral genome-containing nucleocapsids. Studies on the stability of existing viral capsids suggest that the IL-6 effect on the reduction of genome-containing nucleocapsids is mediated through the prevention of the formation of genome-containing nucleocapsids, which is similar to the effect of interferons. However, IFN-α/β and IFN-γ did not participate in the IL-6-induced suppression of HBV replication. Taken together, our results will provide important information to better understand the role of IL-6 in the course of HBV infection.
IRSS: a web-based tool for automatic layout and analysis of IRES secondary structure prediction and searching system in silico
Authors: Wu Tzong-Yuan , Hsieh Chi-Chun , Hong Jun-Jie , Chen Chung-Yung , Tsai Yuh-Show 
Published: May 2009

Abstract

Background
Internal ribosomal entry sites (IRESs) provide alternative, cap-independent translation initiation sites in eukaryotic cells. IRES elements are important factors in viral genomes and are also useful tools for bi-cistronic expression vectors. Most existing RNA structure prediction programs are unable to deal with IRES elements.

Results
We designed an IRES search system, named IRSS, to obtain better results for IRES prediction. RNA secondary structure prediction and comparison software programs were implemented to construct our two-stage strategy for the IRSS. Two software programs formed the backbone of IRSS: the RNAL fold program, used to predict local RNA secondary structures by minimum free energy method; and the RNA Align program, used to compare predicted structures. After complete viral genome database search, the IRSS have low error rate and up to 72.3% sensitivity in appropriated parameters.

Conclusion
IRSS is freely available at this website http://140.135.61.9/ires/. In addition, all source codes, precompiled binaries, examples and documentations are downloadable for local execution. This new search approach for IRES elements will provide a useful research tool on IRES related studies.
Genetic analysis of an F2 intercross between two chicken lines divergently selected for body-weight
Authors: Wahlberg Per , Carlborg Örjan , Foglio Mario , Tordoir Xavier , Syvänen Ann-Christine , Lathrop Mark , Gut Ivo G , Siegel Paul B , Andersson Leif 
Published: May 2009

Abstract

Background
We have performed Quantitative Trait Loci (QTL) analysis of an F2 intercross between two chicken lines divergently selected for juvenile body-weight. In a previous study 13 identified loci with effects on body-weight, only explained a small proportion of the large variation in the F2 population. Epistatic interaction analysis however, indicated that a network of interacting loci with large effect contributed to the difference in body-weight of the parental lines. This previous analysis was, however, based on a sparse microsatellite linkage map and the limited coverage could have affected the main conclusions. Here we present a revised QTL analysis based on a high-density linkage map that provided a more complete coverage of the chicken genome. Furthermore, we utilized genotype data from ~13,000 SNPs to search the genome for potential selective sweeps that have occurred in the selected lines.

Results
We constructed a linkage map comprising 434 genetic markers, covering 31 chromosomes but leaving seven microchromosomes uncovered. The analysis showed that seven regions harbor QTL that influence growth. The pair-wise interaction analysis identified 15 unique QTL pairs and notable is that nine of those involved interactions with a locus on chromosome 7, forming a network of interacting loci. The analysis of ~13,000 SNPs showed that a substantial proportion of the genetic variation present in the founder population has been lost in either of the two selected lines since ~60% of the SNPs polymorphic among lines showed fixation in one of the lines. With the current marker coverage and QTL map resolution we did not observe clear signs of selective sweeps within QTL intervals.

Conclusion
The results from the QTL analysis using the new improved linkage map are to a large extent in concordance with our previous analysis of this pedigree. The difference in body-weight between the parental chicken lines is caused by many QTL each with a small individual effect. Although the increased chromosomal marker coverage did not lead to the identification of additional QTL, we were able to refine the localization of QTL. The importance of epistatic interaction as a mechanism contributing significantly to the remarkable selection response was further strengthened because additional pairs of interacting loci were detected with the improved map.
Intravitreal NGF administration counteracts retina degeneration after permanent carotid artery occlusion in rat
Authors: Sivilia Sandra , Giuliani Alessandro , Fernández Mercedes , Turba Maria Elena , Forni Monica , Massella Alessandro , De Sordi Nadia , Giardino Luciana , Calzà Laura 
Published: May 2009

Abstract

Background
The neurotrophin nerve growth factor (NGF) is produced by different cell types in the anterior and posterior eye, exerting a neuroprotective role in the adult life. The visual system is highly sensitive to NGF and the retina and optic nerve provides suitable subjects for the study of central nervous system degeneration. The model of bilateral carotid occlusion (two-vessel occlusion, 2VO) is a well-established model for chronic brain hypoperfusion leading to brain capillary pathology, to retina and optic nerve degeneration. In order to study if a single intravitreal injection of NGF protects the retina and the optic nerve from degeneration during systemic circulatory diseases, we investigated morphological and molecular changes occurring in the retina and optic nerve of adult rats at different time-points (8, 30 and 75 days) after bilateral carotid occlusion.

Results
We demonstrated that a single intravitreal injection of NGF (5 μg/3 μl performed 24 hours after 2VO ligation) has a long-lasting protective effect on retina and optic nerve degeneration. NGF counteracts retinal ganglion cells degeneration by early affecting Bax/Bcl-2 balance- and c-jun- expression (at 8 days after 2VO). A single intravitreal NGF injection regulates the demyelination/remyelination balance after ischemic injury in the optic nerve toward remyelination (at 75 days after 2VO), as indicated by the MBP expression regulation, thus preventing optic nerve atrophy and ganglion cells degeneration. At 8 days, NGF does not modify 2VO-induced alteration in VEFG and related receptors mRNA expression.

Conclusion
The protective effect of exogenous NGF during this systemic circulatory disease seems to occur also by strengthening the effect of endogenous NGF, the synthesis of which is increased by vascular defect and also by the mechanical lesion associated with NGF or even vehicle intraocular delivery.
Elevated HIV risk behaviour among recently incarcerated injection drug users in a Canadian setting: a longitudinal analysis
Authors: Milloy M-J S , Buxton Jane , Wood Evan , Li Kathy , Montaner Julio SG , Kerr Thomas 
Published: May 2009

Abstract

Background
While incarceration has consistently been associated with a higher risk of HIV infection for individuals who use injection drugs (IDU), the effect of incarceration on the post-release risk environment remains poorly described. We sought to assess the impact of incarceration on risk factors for HIV infection after release from prison in a sample of active IDU in Vancouver, Canada.

Methods
Using a prospective cohort of community-recruited IDU followed from May 1, 1996 to November 30, 2005, we examined contingency tables and performed linear growth curve analyses to assess changes in the prevalence of independent risk factors for HIV infection from before to after a period of incarceration among participants reporting incarceration and a matched control group.

Results
Of the 1603 participants followed-up over the study period, 147 (9.2%) were eligible for an analysis of post-incarceration risk behaviours and 742 (46.3%) were used as matched controls. Significant differences were found in one or both groups for the prevalence of frequent cocaine injection, requiring help injecting, binge drug use, residence in the HIV outbreak epicentre, sex-trade participation and syringe sharing (all p < 0.05) after incarceration. In linear growth curve adjusted for age, gender and ethnicity, syringe sharing was significantly more common in those recently released from prison (p = 0.03) than in the control group.

Conclusion
In a sample of Canadian IDU, we did not observe any effect of incarceration on the prevalence of several behaviours that are risk factors for HIV infection, including intensity of drug use or participation in the sex trade. However, those recently released from prison were more likely to report syringe sharing that those in a matched control group.
The management of neuropathic ulcers of the foot in diabetes by shock wave therapy
Authors: Moretti Biagio , Notarnicola Angela , Maggio Giulio , Moretti Lorenzo , Pascone Michele , Tafuri Silvio , Patella Vittorio 
Published: May 2009

Abstract

Background
Diabetes is becoming one of the most common chronic diseases, and ulcers are its most serious complication. Beginning with neuropathy, the subsequent foot wounds frequently lead to lower extremity amputation, even in the absence of critical limb ischemia. In recent years, some researchers have studied external shock wave therapy (ESWT) as a new approach to soft tissue wound healing. The rationale of this study was to evaluate if ESWT is effective in the management of neuropathic diabetic foot ulcers.

Methods
We designed a randomized, prospective, controlled study in which we recruited 30 patients affected by neuropathic diabetic foot ulcers and then divided them into two groups based on different management strategies. One group was treated with standard care and shock wave therapy. The other group was treated with only standard care. The healing of the ulcers was evaluated over 20 weeks by the rate of re-epithelization.

Results
After 20 weeks of treatment, 53.33% of the ESWT-treated patients had complete wound closure compared with 33.33% of the control patients, and the healing times were 60.8 and 82.2 days, respectively (p < 0.001). Significant differences in the index of the re-epithelization were observed between the two groups, with values of 2.97 mm2/die in the ESWT-group and 1.30 mm2/die in the control group (p < 0.001).

Conclusion
Therefore, ESWT may be a useful adjunct in the management of diabetic foot ulceration.

Trial registration
Current Controlled Trials ISRCTN21800909
State diagrams of the heart – a new approach to describing cardiac mechanics
Authors: Larsson Matilda , Bjällmark Anna , Johnson Jonas , Winter Reidar , Brodin Lars-Åke , Lundbäck Stig 
Published: May 2009

Abstract

Background
Cardiac time intervals have been described as a measure of cardiac performance, where prolongation, shortening and delay of the different time intervals have been evaluated as markers of cardiac dysfunction. A relatively recently developed method with improved ability to measure cardiac events is Tissue Doppler Imaging (TDI), allowing accurate measurement of myocardial movements.

Methods
We propose the state diagram of the heart as a new visualization tool for cardiac time intervals, presenting comparative, normalized data of systolic and diastolic performance, providing a more complete overview of cardiac function. This study aimed to test the feasibility of the state diagram method by presenting examples demonstrating its potential use in the clinical setting and by performing a clinical study, which included a comparison of the state diagram method with established echocardiography methods (E/E' ratio, LVEF and WMSI). The population in the clinical study consisted of seven patients with non ST-elevation myocardial infarction (NSTEMI) and seven control subjects, individually matched according to age and gender. The state diagram of the heart was generated from TDI curves from seven positions in the myocardium, visualizing the inter- and intraventricular function of the heart by displaying the cardiac phases.

Results
The clinical examples demonstrated that the state diagram allows for an intuitive visualization of pathological patterns as ischemia and dyssynchrony. Further, significant differences in percentage duration between the control group and the NSTEMI group were found in eight of the totally twenty phases (10 phases for each ventricle), e.g. in the transition phases (Pre-Ejection and Post-Ejection). These phases were significantly longer (> 2.18%) for the NSTEMI group than for the control group (p < 0.05). No significant differences between the groups were found for the established echocardiography methods.

Conclusion
The test results clearly indicate that the state diagram has potential to be an efficient tool for visualization of cardiac dysfunction and for detection of NSTEMI.
Low levels of amyloid-beta and its transporters in neonatal rats with and without hydrocephalus
Authors: Deren Kelley E , Forsyth Jennifer , Abdullah Osama , Hsu Edward W , Klinge Petra M , Silverberg Gerald D , Johanson Conrad E , McAllister James P 
Published: May 2009

Abstract

Background
Previous studies in aging animals have shown that amyloid-beta protein (Aβ) accumulates and its transporters, low-density lipoprotein receptor-related protein-1 (LRP-1) and the receptor for advanced glycation end products (RAGE) are impaired during hydrocephalus. Furthermore, correlations between astrocytes and Aβ have been found in human cases of normal pressure hydrocephalus (NPH) and Alzheimer's disease (AD). Because hydrocephalus occurs frequently in children, we evaluated the expression of Aβ and its transporters and reactive astrocytosis in animals with neonatal hydrocephalus.

Methods
Hydrocephalus was induced in neonatal rats by intracisternal kaolin injections on post-natal day one, and severe ventriculomegaly developed over a three week period. MRI was performed on post-kaolin days 10 and 21 to document ventriculomegaly. Animals were sacrificed on post-kaolin day 21. For an age-related comparison, tissue was used from previous studies when hydrocephalus was induced in a group of adult animals at either 6 months or 12 months of age. Tissue was processed for immunohistochemistry to visualize LRP-1, RAGE, Aβ, and glial fibrillary acidic protein (GFAP) and with quantitative real time reverse transcriptase polymerase chain reaction (qRT-PCR) to quantify expression of LRP-1, RAGE, and GFAP.

Results
When 21-day post-kaolin neonatal hydrocephalic animals were compared to adult (6–12 month old) hydrocephalic animals, immunohistochemistry demonstrated levels of Aβ, RAGE, and LRP-1 that were substantially lower in the younger animals; in contrast, GFAP levels were elevated in both young and old hydrocephalic animals. When the neonatal hydrocephalic animals were compared to age-matched controls, qRT-PCR demonstrated no significant changes in Aβ, LRP-1 and RAGE. However, immunohistochemistry showed very small increases or decreases in individual proteins. Furthermore, qRT-PCR indicated statistically significant increases in GFAP.

Conclusion
Neonatal rats with and without hydrocephalus had low expression of Aβ and its transporters when compared to adult rats with hydrocephalus. No statistical differences were observed in Aβ and its transporters between the control and hydrocephalic neonatal animals.
Over 50 years of trial in Acta Psychiatrica Scandinavica: a survey
Authors: Matar Hosam E , Almerie Muhammad Q , Al Marhi Muhammad O , Adams Clive E 
Published: May 2009

Abstract

Background
Randomised controlled trials are the gold standard for evaluating mental health care interventions. We assessed the content and quality of trials published in Acta Psychiatrica Scandinavica and Supplementum since 1948.

Methods
All trials were identified manually, quality assessed, data extracted, and sought on Medline.

Results
About 8.6% of all reports in the journal were clinical trials (n = 582) with the peak frequency in the 1980s. Most originate from Europe (80%) and focus on depression (~38%) or schizophrenia (27%). The median sample size is 44. We found only two trials that fully met the criteria of quality reporting RCTs set by CONSORT statements (0.34%) since 1996. Less than 50% of records were possible to identify by a Medline search using broad methodological terms.

Conclusion
Acta is a major source of health trials. The standard of reporting is similar to other journals but better adherence to CONSORT would ensure higher quality of reports and better dissemination.
Hypermethylation of genomic 3.3-kb repeats is frequent event in HPV-positive cervical cancer
Authors: Katargin Alexey N , Pavlova Larissa S , Kisseljov Fjodor L , Kisseljova Natalia P 
Published: May 2009

AbstractBackgroundLarge-scale screening methods are widely used to reveal cancer-specific DNA methylation markers. We previously identified non-satellite 3.3-kb repeats associated with facioscapulohumeral muscular dystrophy (FSHD) as hypermethylated in cervical cancer in genome-wide screening. To determine whether hypermethylation of 3.3-kb repeats is a tumor-specific event and to evaluate frequency of this event in tumors, we investigated the 3.3-kb repeat methylation status in human papilloma virus (HPV)-positive cervical tumors, cancer cell lines, and normal cervical tissues. Open reading frames encoding DUX family proteins are contained within some 3.3-kb repeat units. TheDUXmRNA expression profile was also studied in these tissues.MethodsThe methylation status of 3.3-kb repeats was evaluated by Southern blot hybridization and bisulfite genomic sequencing. The expression ofDUXmRNA was analyzed by RT-PCR and specificity of PCR products was confirmed by sequencing analysis.ResultsHypermethylation of 3.3-kb repeats relative to normal tissues was revealed for the first time in more than 50% (18/34) of cervical tumors and in 4 HPV-positive cervical cancer cell lines. Hypermethylation of 3.3-kb repeats was observed in tumors concurrently with or independently of hypomethylation of classical satellite 2 sequences (Sat2) that were hypomethylated in 75% (15/20) of cervical tumors. We have revealed the presence of transcripts highly homologous toDUX4andDUX10genes in normal tissues and down-regulation of transcripts in 68% of tumors with and without 3.3-kb repeats hypermethylation.ConclusionOur results demonstrate that hypermethylation rather than hypomethylation of 3.3-kb repeats is the predominant event in HPV-associated cervical cancer and provide new insight into the epigenetic changes of repetitive DNA elements in carcinogenesis.