bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiovascular Risk Attributable to Diabetes in Southern Brazil
Authors: Moreira Leila B. , Fuchs Sandra C. , Wiehe Mário , Neyeloff Jeruza L. , Picon Rafael V. , Moreira Marina B. , Gus Miguel , Fuchs Flávio D. 
Published: February 2009

OBJECTIVE
To analyze the effect of diabetes on general and cardiovascular disease (CVD) mortality and morbidity in southern Brazil.

RESEARCH DESIGN AND METHODS
A population-based cohort study of 1,091 individuals was conducted. Diabetes was ascertained by medical history. The vital status of 982 individuals and the incidence of events were ascertained during another visit and through hospital records, death certificates, and verbal necropsy with relatives.

RESULTS
The mean ± SD age of participants was 43.1 ± 17 years, and 55.7% were women. The prevalence of diabetes was 4.2%, and the mean follow-up time was 5.3 ± 0.07 years. Mortality was 36.3% and 6.6% in participants with or without diabetes, respectively; the incidence of CVD was 20.8% and 3.0%, with an adjusted hazard ratio of 4.4 (95% CI 2.4–7.9). Diabetic population-attributable risk (PAR) for CVD mortality was 10.1% and 13.1% for total CVD.

CONCLUSIONS
Diabetes is responsible for a large PAR for overall mortality and cardiovascular events in Brazil.
Continuity and Change in Glycemic Control Trajectories From Adolescence to Emerging Adulthood
Authors: Luyckx Koen , Seiffge-Krenke Inge 
Published: February 2009

OBJECTIVE
To determine developmental classes of glycemic control in young people with type 1 diabetes throughout adolescence and emerging adulthood and assess relationships with general family climate and self-concept.

RESEARCH DESIGN AND METHODS
In an eight-wave longitudinal study, 72 individuals (37 females) completed questionnaires assessing family climate (at times 1–4) and self-concept (at times 1–4 and 6). Times 1–4 covered adolescence (mean ages were 14–17 years, respectively); times 5–8 covered emerging adulthood (mean ages were 21–25 years, respectively). At each time point, patients visited their physicians to determine A1C values, and questionnaires were sent to the physicians to obtain these values. Latent class growth analysis was used to identify developmental classes of glycemic control.

RESULTS
Latent class growth analysis favored a three-class solution, consisting of optimal control (n = 10), moderate control (n = 51), and deteriorating control (n = 11). From time 3 on and especially during emerging adulthood, mean A1C levels were substantially different among the classes. Additional ANOVAs indicated that at times 1, 2, and 4, the optimal control class was characterized by the most optimal family climate, whereas at times 3, 4, and 6, the deteriorating control class was characterized by the lowest score on positive self-concept.

CONCLUSIONS
From late adolescence on, a multiformity of glycemic control trajectories emerged, which became more diversified throughout emerging adulthood. Family climate and self-concept in mid-to-late adolescence served as psychosocial markers of these developmental classes.
Influence of weekend versus weekday hospital admission on mortality following subarachnoid hemorrhage
Authors: Crowley R. Webster , Yeoh Hian K. , Stukenborg George J. , Ionescu Adina A. , Kassell Neal F. , Dumont Aaron S. 
Published: February 2009

Object
Several studies have indicated that short-term mortality risk is higher among patients who are admitted on the weekends. This “weekend effect” has been observed among patients admitted with a variety of diagnoses, including myocardial infarction, pulmonary embolism, ruptured abdominal aortic aneurysm, and stroke. This study examines the relationship between short-term mortality risk and weekend admission among patients hospitalized following subarachnoid hemorrhage (SAH).

Methods
This retrospective cohort study examines mortality outcomes among patients included in the Nationwide Inpatient Sample (NIS) for 2004. Patients included in the cohort were identified using the International Classification of Diseases, 9th revision, Clinical Modification (ICD-9-CM) code for SAH. Multivariable logistic regression analyses and Cox proportional hazard regression analyses are used to measure the association of weekend admission on mortality for patients with SAH, adjusted for differences in patient characteristics that also contribute to mortality risk.

Results
Weekend admissions occurred among 27.5% of the 5667 patients with SAH in the NIS database. Weekend admission was not a statistically significant independent predictor of death in the SAH study population at 7 days (OR 1.07, 95% CI 0.91–1.25), 14 days (OR 1.01, 95% CI 0.87–1.17), or 30 days (OR 1.03, 95% CI 0.89–1.19).

Conclusions
Weekend admission is not associated with significantly increased short-term mortality risk among patients hospitalized with SAH.
Multispectral molecular imaging of capillary endothelium to facilitate preoperative endovascular brain mapping
Authors: Manning H. Charles , Shay Sheila D. , Mericle Robert A. 
Published: February 2009

Object
Brain mapping aims to localize neurological function to specific regions of the human brain. Preoperative endovascular brain mapping (PEBM) is a novel approach that allows clear visualization of nonfunctional (silent) brain parenchyma in real time during a resection. It has potential to improve neurosurgical guidance because brain shift does not alter the maps, and the map is visualized directly on the brain in situ rather than on a nearby image. Therefore, the risk of a new neurological deficit should be reduced. The authors report the first PEBM approach that combines selective molecular targeting of brain endothelium with multispectral (optical) imaging in preclinical animal models.

Methods
Sprague-Dawley rats and New Zealand white rabbits were selectively catheterized, and a fluorescein isothiocyanate–derivatized tomato lectin–based imaging probe was administered into the carotid artery or posterior cerebral artery, measuring < 500 μm in diameter. After binding/uptake of the imaging probe, and removal of unbound probe, a craniotomy was performed to directly visualize the “brain map.”

Results
Selective localization of the imaging probe to the right hemisphere in rats or right posterior cerebral artery in rabbits was clearly visualized after craniotomy. Cross-sections of stained capillaries demonstrated that the imaging probe did not cause vascular occlusion. Gross regional selectivity of the imaging probe was documented by multispectral molecular imaging of intact brains, with discrete localization and endothelium-directed targeting validated by histological examination.

Conclusions
The authors have demonstrated the first molecular endothelium-targeted approach to PEBM that does not require manipulation of the intact blood-brain barrier or result in vascular occlusion. Furthermore, the presented multispectral molecular imaging technique appears to be a suitable methodology for the generation of region-selective brain maps of vascularized brain parenchyma. Further refinement of the PEBM approach, as well as the development of improved imaging probes, may result in clinical advancement of PEBM where direct visual discrimination of nonfunctional silent brain parenchyma at the time of resection could significantly improve neurosurgical outcomes.
Hemodynamic instability during carotid artery stenting: the relative contribution of stent deployment versus balloon dilation
Authors: Bussière Miguel , Lownie Stephen P. , Lee Donald , Gulka Irene , Leung Andrew , Pelz David M. 
Published: February 2009

Object
Hemodynamic instability may complicate carotid angioplasty and stenting in up to 40% of patients. The authors have previously demonstrated that primary self-expanding stent placement alone can gradually dilate severely stenosed carotid arteries without the use of balloons. The authors hypothesized that eliminating the balloon would reduce carotid baroreceptor stimulation, thereby decreasing the incidence of hemodynamic instability.

Methods
Ninety-seven high surgical risk patients with symptomatic, severely stenosed carotid arteries were treated with the intention of using a self-expanding stent alone. Seventy-seven arteries (79%) were treated with stenting alone, and 20 required angioplasty (21%).

Results
Intraprocedural bradycardia (heart rate < 60 bpm) developed in 29 patients (38%) and hypotension (systolic blood pressure < 90 mm Hg) occurred in 1 patient (1%) treated with stenting alone. Fourteen patients (70%) who underwent angioplasty and stenting had bradycardia, and hypotension developed in 4 (20%). Atropine, glycopyrrolate, or vasopressors were required in 8% of patients who received stenting alone, compared to 30% of patients who underwent angioplasty. In the first 24 hours after treatment, hypotension or bradycardia developed in 25 patients (32%) who had undergone stent placement alone, and in 15 patients (75%) after stent placement and balloon angioplasty. There was no difference in the occurrence of intra- or postprocedural hypertension (systolic blood pressure > 160 mm Hg) between patients treated with stenting alone or stenting and balloons. Factors independently associated with hemodynamic depression included baseline heart rate and balloon use.

Conclusions
Hemodynamic instability during and after carotid artery stenting was observed more frequently when balloon angioplasty was required than when stent placement was performed without concurrent balloon angioplasty.
HIV-1 Tat Addresses Dendritic Cells to Induce a Predominant Th1-Type Adaptive Immune Response That Appears Prevalent in the Asymptomatic Stage of Infection
Authors: Fanales-Belasio Emanuele , Moretti Sonia , Fiorelli Valeria , Tripiciano Antonella , Pavone Cossut Maria R. , Scoglio Arianna , Collacchi Barbara , Nappi Filomena , Macchia Iole , Bellino Stefania , Francavilla Vittorio , Caputo Antonella , Barillari Giovanni , Magnani Mauro , Laguardia Maria Elena , Cafaro Aurelio , Titti Fausto , Monini Paolo , Ensoli Fabrizio , Ensoli Barbara 
Published: February 2009

Abstract
Tat is an early regulatory protein that plays a major role in human HIV-1 replication and AIDS pathogenesis, and therefore, it represents a key target for the host immune response. In natural infection, however, Abs against Tat are produced only by a small fraction (∼20%) of asymptomatic individuals and are rarely seen in progressors, suggesting that Tat may possess properties diverting the adaptive immunity from generating humoral responses. Here we show that a Th1-type T cell response against Tat is predominant over a Th2-type B cell response in natural HIV-1 infection. This is likely due to the capability of Tat to selectively target and very efficiently enter CD1a-expressing monocyte-derived dendritic cells (MDDC), which represent a primary target for the recognition and response to virus Ag. Upon cellular uptake, Tat induces MDDC maturation and Th1-associated cytokines and β-chemokines production and polarizes the immune response in vitro to the Th1 pattern through the transcriptional activation of TNF-α gene expression. This requires the full conservation of Tat transactivation activity since neither MDDC maturation nor TNF-α production are found with either an oxidized Tat, which does not enter MDDC, or with a Tat protein mutated in the cysteine-rich region (cys22 Tat), which enters MDDC as the wild-type Tat but is transactivation silent. Consistently with these data, inoculation of monkeys with the native wild-type Tat induced a predominant Th1 response, whereas cys22 Tat generated mostly Th2 responses, therefore providing evidence that Tat induces a predominant Th1 polarized adaptive immune response in the host.
Human Dendritic Cells Produce TGF-β1 under the Influence of Lung Carcinoma Cells and Prime the Differentiation of CD4+CD25+Foxp3+ Regulatory T Cells
Authors: Dumitriu Ingrid E. , Dunbar Donald R. , Howie Sarah E. , Sethi Tariq , Gregory Christopher D. 
Published: February 2009

Abstract
Dendritic cells (DCs) have a central role in the development of adaptive immune responses, including antitumor immunity. Factors present in the tumor milieu can alter the maturation of DCs and inhibit their capacity to activate T cells. Using gene expression analysis, we found that human DCs increased the expression of TGF-β1 transcripts following culture with human lung carcinoma cells (LCCs). These DCs produced increased amounts of TGF-β1 protein compared with DCs not exposed to tumor cells. LCCs also decreased the expression of CD86 and HLA-DR by immature DCs. Furthermore, LCCs decreased CD86 expression and the production of TNF-α and IL-12 p70 by mature DCs. Moreover, LCCs also converted mature DCs into cells producing TGF-β1. These TGF-β1-producing DCs were poor at eliciting the activation of naive CD4+ T cells and sustaining their proliferation and differentiation into Th1 (IFN-γ+) effectors. Instead, TGF-β1-producing DCs demonstrated an increased ability to generate CD4+CD25+Foxp3+ regulatory T cells that suppress the proliferation of T lymphocytes. These results identify a novel mechanism by which the function of human DCs is altered by tumor cells and contributes to the evasion of the immune response.
Inhibition of CCR6 Function Reduces the Severity of Experimental Autoimmune Encephalomyelitis via Effects on the Priming Phase of the Immune Response
Authors: Liston Adrian , Kohler Rachel E. , Townley Scott , Haylock-Jacobs Sarah , Comerford Iain , Caon Adriana C. , Webster Julie , Harrison Jodie M. , Swann Jeremy , Clark-Lewis Ian , Korner Heinrich , McColl Shaun R. 
Published: February 2009

Abstract
Chemokines are essential for homeostasis and activation of the immune system. The chemokine ligand/receptor pairing CCL20/CCR6 is interesting because these molecules display characteristics of both homeostatic and activation functions. These dual characteristics suggest a role for CCR6 in the priming and effector phases of the immune response. However, while CCR6 has been implicated in the effector phase in several models, a role in the priming phase is less clear. Herein we analyze the role of CCR6 in these two important arms of the immune response during experimental autoimmune encephalomyelitis (EAE). Both CCR6 and its chemokine ligand CCL20 were up-regulated in the draining lymph nodes and spinal cord during EAE, and CCR6 was up-regulated on CD4+ T cells that had divided following induction of EAE. The functional role of this expression was demonstrated by impaired development of EAE in gene-targeted CCR6-deficient mice and in mice treated either with a neutralizing anti-CCR6 Ab or with a novel receptor antagonist. Inhibition of EAE was due to reduced priming of autoreactive CD4+ T cells probably as a result of impaired late-stage influx of dendritic cells into draining lymph nodes. This was accompanied by reduced egress of activated lymphocytes from the lymph nodes. These results demonstrate a novel role for CCR6 in the mechanism of autoreactive lymphocyte priming and emigration to the efferent lymphatics.
IL-17 Promotes Progression of Cutaneous Leishmaniasis in Susceptible Mice
Authors: Lopez Kostka Susanna , Dinges Stephanie , Griewank Klaus , Iwakura Yoichiro , Udey Mark C. , von Stebut Esther 
Published: February 2009

Abstract
Resistance to leishmaniasis in C57BL/6 mice depends on Th1/Tc1 cells. BALB/c mice preferentially develop Th2 immunity and succumb to infection. We now assessed the role of IL-17 in cutaneous leishmaniasis. During the course of Leishmania major infection, BALB/c CD4 cells and neutrophils produced increased amounts of IL-17 as compared with cells from C57BL/6 mice. This increase was associated with significantly increased IL-23 release from L. major-infected BALB/c dendritic cells (DC), whereas IL-6 and TGF-β1 production by BALB/c and C57BL/6 DC were comparable. Interestingly, lesion sizes in infected IL-17-deficient BALB/c mice were dramatically smaller and failed to progress as compared with those in control mice. Similar amounts of IL-4, IL-10, and IFN-γ were produced by T cells from IL-17-deficient mice and control mice consistent with development of Th2-predominant immunity in all animals. Improved disease outcome was associated with decreased CXCL2-accumulation in lesion sites and decreased neutrophil immigration into lesions of infected IL-17-deficient mice confirming prior observations that enhanced neutrophil recruitment contributes to disease susceptibility in BALB/c mice. This study excludes an important facilitating role for IL-17 in Th1/Th2 development in L. major-infected BALB/c mice, and suggests that IL-23 production by L. major-infected DC maintains IL-17+ cells that influence disease progression via regulation of neutrophil recruitment.
Stabilized β-Catenin in Thymic Epithelial Cells Blocks Thymus Development and Function
Authors: Zuklys Saulius , Gill Jason , Keller Marcel P. , Hauri-Hohl Mathias , Zhanybekova Saule , Balciunaite Gina , Na Kyung-Jae , Jeker Lukas T. , Hafen Katrin , Tsukamoto Noriyuki , Amagai Takashi , Taketo Makoto M. , Krenger Werner , Holländer Georg A. 
Published: February 2009

Abstract
Thymic T cell development is dependent on a specialized epithelial microenvironment mainly composed of cortical and medullary thymic epithelial cells (TECs). The molecular programs governing the differentiation and maintenance of TECs remain largely unknown. Wnt signaling is central to the development and maintenance of several organ systems but a specific role of this pathway for thymus organogenesis has not yet been ascertained. In this report, we demonstrate that activation of the canonical Wnt signaling pathway by a stabilizing mutation of β-catenin targeted exclusively to TECs changes the initial commitment of endodermal epithelia to a thymic cell fate. Consequently, the formation of a correctly composed and organized thymic microenvironment is prevented, thymic immigration of hematopoietic precursors is restricted, and intrathymic T cell differentiation is arrested at a very early developmental stage causing severe immunodeficiency. These results suggest that a precise regulation of canonical Wnt signaling in thymic epithelia is essential for normal thymus development and function.
Tumor-Specific Bacteriophages Induce Tumor Destruction through Activation of Tumor-Associated Macrophages
Authors: Eriksson Fredrik , Tsagozis Panagiotis , Lundberg Kajsa , Parsa Roham , Mangsbo Sara M. , Persson Mats A. A. , Harris Robert A. , Pisa Pavel 
Published: February 2009

Abstract
We recently reported that administration of tumor-specific bacteriophages initiates infiltration of neutrophilic granulocytes with subsequent regression of established B16 tumors. The aim of the current study was to investigate the mechanism of action of bacteriophage-induced tumor regression and to examine possible stimulatory effects of bacteriophages on macrophages. We observed that the mechanism of phage-induced tumor regression is TLR dependent as no signs of tumor destruction or neutrophil infiltration were observed in tumors in MyD88−/− mice in which TLR signaling is abolished. The microenvironment of bacteriophage-treated tumors was further analyzed by gene profiling through applying a low-density array preferentially designed to detect genes expressed by activated APCs, which demonstrated that the M2-polarized tumor microenvironment switched to a more M1-polarized milieu following phage treatment. Bacteriophage stimulation induced secretion of proinflammatory cytokines in both normal mouse macrophages and tumor-associated macrophages (TAMs) and increased expression of molecules involved in Ag presentation and costimulation. Furthermore, mouse neutrophils selectively migrated toward mediators secreted by bacteriophage-stimulated TAMs. Under these conditions, the neutrophils also exhibited increased cytotoxicity toward B16 mouse melanoma target cells. These results describe a close interplay of the innate immune system in which bacteriophages, located to the tumor microenvironment due to their specificity, stimulate TAMs to secrete factors that promote recruitment of neutrophils and potentiate neutrophil-mediated tumor destruction.
ELR-CXC Chemokine Receptor Antagonism Targets Inflammatory Responses at Multiple Levels
Authors: Zhao Xixing , Town Jennifer R. , Li Fang , Zhang Xiaobei , Cockcroft Donald W. , Gordon John R. 
Published: February 2009

AbstractThe ELR-CXC chemokines play important roles in neutrophilic inflammation. We report in this study that a fully human ELR-CXC chemokine antagonist that we have generated, CXCL8(3–72)K11R/G31P (G31P), has potent anti-inflammatory effects that arise through its actions at multiple levels. G31P inhibited CXCL8-induced chemotactic responses and intracellular Ca2+ flux in CXCR1-transfected HEK cells and neutrophils, and responses of neutrophils to CXCR2-exclusive ligands. G31P desensitized heterologous G protein-coupled receptors on neutrophils, 52–86% reducing their Ca2+ flux and chemotactic responses to leukotriene B4, C5a, and the bacterial tripeptide fMLP. G31P also 60–90% blocked neutrophil chemotactic responses to mediators present in 10 of 12 sputum samples from cystic fibrosis or bronchiectasis subjects with bacterial pneumonia. Moreover, whereas A549 bronchial epithelial cells (which expressed CXCR1) secreted ≈29,000 pg/ml CXCL8 in response to in vitro endotoxin challenge, G31P reduced this response by up to 98%, presumably by interrupting an autocrine inflammatory loop. The anti-inflammatory effects of G31P extended also to reversing the antiapoptotic influence of ELR-CXC chemokines on neutrophils. That these effects were relevant in vivo was confirmed in a guinea pig model of airway endotoxemia, wherein the human form of G31P &gt;95% blocked neutrophil infiltration into and activation within the airways, as determined by airway levels of the neutrophil primary, secondary, and tertiary granule markers myeloperoxidase, lactoferrin, and matrix metalloproteinase-9, respectively, and the epithelial cell marker matrix metalloproteinase-2. These data suggest that the beneficial effects of ELR-CXC chemokine antagonism arise through effects that occur at multiple levels, including epithelial cells, neutrophils, and alternate G protein-coupled receptors.
An Unusual Insertion in Jak2 Is Crucial for Kinase Activity and Differentially Affects Cytokine Responses
Authors: Haan Claude , Kroy Daniela C. , Wüller Stefan , Sommer Ulrike , Nöcker Tanja , Rolvering Catherine , Behrmann Iris , Heinrich Peter C. , Haan Serge 
Published: February 2009

Abstract
The Janus kinases, Jaks, constitutively associate with the cytoplasmic region of cytokine receptors and play an important role in a multitude of biological processes. Jak2 dysfunction has been implicated in myeloproliferative diseases and leukemia. Although Jaks were studied extensively for many years, the molecular mechanism of Jak activation upon cytokine stimulation of cells is still incompletely understood. In this study, we investigated the importance of an unusual insertion located within the kinase domain in Jak2. We found that the deletion of this insertion, which we named the Jak-specific insertion (JSI), totally abrogates Jak2 autophosphorylation. We further point mutated four residues within the JSI that are conserved in all Jak family members. Three of these mutants showed abrogated or reduced autophosphorylation, whereas the fourth displayed increased autophosphorylation. We found that the phosphorylation state of these mutants is not influenced by other domains of the kinase. Our data further suggest that the JSI is not required for the negative regulation of kinase activity by the suppressor of cytokine signaling proteins, SOCS. Most importantly, we show that mutations in this region differentially affect IFN-γ and erythropoietin signal transduction. Taken together, the dramatic effects on the phosphorylation status of Jak2 as well as the differential effects on the signaling via different cytokines highlight the importance of this unusual region for the catalytic activity of Jaks.