bluuebunny/crossref_metadata_2025_split huggingface dataset:
Galectin-1: a key effector of regulation mediated by CD4+CD25+ T cells
Authors: Garín Marina I. , Chu Chung-Ching , Golshayan Dela , Cernuda-Morollón Eva , Wait Robin , Lechler Robert I. 
Published: November 2006

AbstractThe naturally occurring population of dedicated regulatory T cells that coexpress CD4 and CD25 is known to play a key role in the maintenance of peripheral T-cell tolerance; however, their mechanism of action has remained obscure. Here we report that a member of the family of β-galactoside–binding proteins, galectin-1, is overexpressed in regulatory T cells, and that expression is increased after activation. Most importantly, blockade of galectin-1 binding significantly reduced the inhibitory effects of human and mouse CD4+CD25+ T cells. Reduced regulatory activity was observed in CD4+CD25+ T cells obtained from galectin-1–homozygous null mutant mice. These results suggest that galectin-1 is a key effector of the regulation mediated by these cells.
Hypoxia-inducible transcription factor–1 alpha determines sensitivity of endothelial cells to the proteosome inhibitor bortezomib
Authors: Veschini Lorenzo , Belloni Daniela , Foglieni Chiara , Cangi Maria Giulia , Ferrarini Marina , Caligaris-Cappio Federico , Ferrero Elisabetta 
Published: November 2006

AbstractAngiogenesis is a complex, orchestrated process that plays a critical role in several conditions and has special relevance in the progression of cancer. Hypoxia is the major stimulus for angiogenesis, and hypoxia-inducible transcription factor–1 alpha (HIF-1α) is its key mediator. We set up a novel in vitro model of HIF-1α up-regulation by treating human umbilical vein endothelial cells (HUVECs) with the hypoxia-mimicking deferoxamine (DFO) and found that this condition was sufficient to promote angiogenesis, like the well-known HUVEC model cultured under low pO2. The proteasome inhibitor bortezomib, which induces strong apoptosis in cancer cells, abrogated proliferation and angiogenesis of HUVECs when used at a high concentration (100 nM), yet promoted both functions at a low dosage (10 nM). This double-edged effect appeared to be mediated by differential effects exerted by the different concentrations of bortezomib on 2 master regulators of tumor-associated angiogenesis, HIF-1α and nuclear factor kappa B (NF-kB). Significantly, when HUVECs were induced to express HIF-1α prior to bortezomib treatment, proliferative and angiogenic responses were abolished, and a greatly enhanced proapoptotic effect was promoted with both concentrations of the drug. These findings indicate that HIF-1α up-regulation may sensitize endothelial cells to the antiangiogenic and proapoptotic effects of bortezomib and might be exploited to target tumor-associated vessels in the course of antiangiogenic therapies.
Identification of MCL1 as a novel target in neoplastic mast cells in systemic mastocytosis: inhibition of mast cell survival by MCL1 antisense oligonucleotides and synergism with PKC412
Authors: Aichberger Karl J. , Mayerhofer Matthias , Gleixner Karoline V. , Krauth Maria-Theresa , Gruze Alexander , Pickl Winfried F. , Wacheck Volker , Selzer Edgar , Müllauer Leonhard , Agis Hermine , Sillaber Christian , Valent Peter 
Published: November 2006

AbstractMCL-1 is a Bcl-2 family member that has been described as antiapoptotic in various myeloid neoplasms. Therefore, MCL-1 has been suggested as a potential new therapeutic target. Systemic mastocytosis (SM) is a myeloid neoplasm involving mast cells (MCs) and their progenitors. In the present study, we examined the expression and functional role of MCL-1 in neoplastic MCs and sought to determine whether MCL-1 could serve as a target in SM. As assessed by RT-PCR and immunohistochemical examination, primary neoplastic MCs expressed MCL-1 mRNA and the MCL-1 protein in all SM patients examined. Moreover, MCL-1 was detectable in both subclones of the MC line HMC-1—HMC-1.1 cells, which lack the SM-related KIT mutation D816V, and HMC-1.2 cells, which carry KIT D816V. Exposure of HMC-1.1 cells or HMC-1.2 cells to MCL-1–specific antisense oligonucleotides (ASOs) or MCL-1–specific siRNA resulted in reduced survival and increased apoptosis compared with untreated cells. Moreover, MCL-1 ASOs were found to cooperate with various tyrosine kinase inhibitors in producing growth inhibition in neoplastic MCs, with synergistic effects observed with PKC412, AMN107, and imatinib in HMC-1.1 cells and with PKC412 in HMC-1.2 cells. Together, these data show that MCL-1 is a novel survival factor and an attractive target in neoplastic MCs.
The cytoprotective protein C pathway
Authors: Mosnier Laurent O. , Zlokovic Berislav V. , Griffin John H. 
Published: November 2006

AbstractProtein C is best known for its mild deficiency associated with venous thrombosis risk and severe deficiency associated with neonatal purpura fulminans. Activated protein C (APC) anticoagulant activity involves proteolytic inactivation of factors Va and VIIIa, and APC resistance is often caused by factor V Leiden. Less known is the clinical success of APC in reducing mortality in severe sepsis patients (PROWESS trial) that gave impetus to new directions for basic and preclinical research on APC. This review summarizes insights gleaned from recent in vitro and in vivo studies of the direct cytoprotective effects of APC that include beneficial alterations in gene expression profiles, anti-inflammatory actions, antiapoptotic activities, and stabilization of endothelial barriers. APC's cytoprotection requires its receptor, endothelial cell protein C receptor, and protease-activated receptor-1. Because of its pleiotropic activities, APC has potential roles in the treatment of complex disorders, including sepsis, thrombosis, and ischemic stroke. Although much about molecular mechanisms for APC's effects on cells remains unclear, it is clear that APC's structural features mediating anticoagulant actions and related bleeding risks are distinct from those mediating cytoprotective actions, suggesting the possibility of developing APC variants with an improved profile for the ratio of cytoprotective to anticoagulant actions.
Leukocytosis is a risk factor for thrombosis in essential thrombocythemia: interaction with treatment, standard risk factors, and Jak2 mutation status
Authors: Carobbio Alessandra , Finazzi Guido , Guerini Vittoria , Spinelli Orietta , Delaini Federica , Marchioli Roberto , Borrelli Giovanna , Rambaldi Alessandro , Barbui Tiziano 
Published: November 2006

AbstractLeukocytes contribute to the pathogenesis of thrombosis in essential thrombocythemia (ET) through recently discovered mechanisms of activation and interaction with platelets and endothelial cells. To evaluate whether an increased leukocyte count was associated with thrombosis and whether this effect can be modulated by therapy, we analyzed the clinical course of 439 patients with ET followed at the Ospedali Riuniti di Bergamo. The strength of the association was measured at diagnosis or before thrombotic events by multivariable analyses carried out using data at baseline as well as time-varying covariates. The results showed that (1) an increased leukocyte count at diagnosis was associated with thrombosis during follow-up (“baseline analysis,” relative risk [RR] 2.3, 95% confidence interval [CI] 1.4-3.9, P = .001); (2) hydroxyurea (HU) lowered leukocytosis and reduced the strength of the association between leukocytosis and thrombosis (“time-dependent analysis,” RR 1.6, 95% CI 0.9-2.0, not significant [NS]); (3) the association of leukocytosis and thrombosis was more evident in untreated low-risk patients (RR 2.7, 95% CI 1.2-6.4, P = .01) compared with HU-treated high-risk patients (RR 1.6, 95% CI 0.8-3.2, NS); and (4) the presence of JAK2 V617F was not identified as a risk factor for thrombosis during follow-up despite a significant association between the mutation and leukocytosis. We suggest validation of these findings in prospective clinical studies.
Vitamin K supplementation can improve stability of anticoagulation for patients with unexplained variability in response to warfarin
Authors: Sconce Elizabeth , Avery Peter , Wynne Hilary , Kamali Farhad 
Published: November 2006

Abstract
Patients receiving warfarin who have unstable control of anticoagulation have a significantly lower intake of dietary vitamin K compared with their stable counterparts. We hypothesized that supplementation with oral vitamin K would improve stability in patients with previously unstable control of anticoagulation. Seventy warfarin-treated patients with unstable anticoagulation control were randomly assigned in a double-blinded fashion to receive a daily amount of 150 μg oral vitamin K or placebo orally for 6 months. Measures of stability of anticoagulation control in the 6-month study period were compared with those in the 6 months immediately prior to it. Vitamin K supplementation resulted in a significantly greater decrease in standard deviation of international normalized ratio (INR) compared with placebo (−0.24 ± 0.14 vs −0.11 ± 0.18; P < .001) and a significantly greater increase in percentage time within target INR range (28% ± 20% vs 15% ± 20%; P < .01). Anticoagulation control improved in 33 of 35 patients receiving vitamin K supplementation; of these, 19 fulfilled our criteria for having stable control of anticoagulation. However, only 24 of 33 patients receiving placebo demonstrated some degree of improvement, with only 7 patients fulfilling the criteria for having stable control. Concomitant supplementation of vitamin K, perhaps through reducing the relative day-to-day variability in dietary vitamin K intake, can significantly improve anticoagulation control in patients with unexplained instability of response to warfarin.
Visual setup of logical models of signaling and regulatory networks with ProMoT
Authors: Saez-Rodriguez Julio , Mirschel Sebastian , Hemenway Rebecca , Klamt Steffen , Gilles Ernst Dieter , Ginkel Martin 
Published: November 2006

Abstract

Background
The analysis of biochemical networks using a logical (Boolean) description is an important approach in Systems Biology. Recently, new methods have been proposed to analyze large signaling and regulatory networks using this formalism. Even though there is a large number of tools to set up models describing biological networks using a biochemical (kinetic) formalism, however, they do not support logical models.

Results
Herein we present a flexible framework for setting up large logical models in a visual manner with the software tool ProMoT. An easily extendible library, ProMoT's inherent modularity and object-oriented concept as well as adaptive visualization techniques provide a versatile environment. Both the graphical and the textual description of the logical model can be exported to different formats.

Conclusion
New features of ProMoT facilitate an efficient set-up of large Boolean models of biochemical interaction networks. The modeling environment is flexible; it can easily be adapted to specific requirements, and new extensions can be introduced. ProMoT is freely available from http://www.mpi-magdeburg.mpg.de/projects/promot/.
Transcription factor 7-like 2 (TCF7L2) variant is associated with familial breast cancer risk: a case-control study
Authors: Burwinkel Barbara , Shanmugam Kalai S , Hemminki Kari , Meindl Alfons , Schmutzler Rita K , Sutter Christian , Wappenschmidt Barbara , Kiechle Marion , Bartram Claus R , Frank Bernd 
Published: November 2006

Abstract

Background
The transcription factor 7-like 2 (TCF7L2) is a critical component of the Wnt/β-catenin pathway. Aberrant TCF7L2 expression modifies Wnt signaling and mediates oncogenic effects through the upregulation of c-MYC and cyclin D. Genetic alterations in TCF7L2 may therefore affect cancer risk. Recently, TCF7L2 variants, including the microsatellite marker DG10S478 and the nearly perfectly linked SNP rs12233372, were identified to associate with type 2 diabetes.

Methods
We investigated the effect of the TCF7L2 rs12255372 variant on familial breast cancer (BC) risk by means of TaqMan allelic discrimination, analyzing BRCA1/2 mutation-negative index patients of 592 German BC families and 735 control individuals.

Results
The T allele of rs12255372 showed an association with borderline significance (OR = 1.19, 95% C.I. = 1.01-1.42, P = 0.04), and the Cochran-Armitage test for trend revealed an allele dose-dependent association of rs12255372 with BC risk (P
trend = 0.04).

Conclusion
Our results suggest a possible influence of TCF7L2 rs12255372 on the risk of familial BC.
The CENP-B homolog, Abp1, interacts with the initiation protein Cdc23 (MCM10) and is required for efficient DNA replication in fission yeast
Authors: Locovei Alexandra M , Spiga Maria-Grazia , Tanaka Katsunori , Murakami Yota , D'Urso Gennaro 
Published: November 2006

Abstract
Abp1, and the closely related Cbh1 and Cbh2 are homologous to the human centromere-binding protein CENP-B that has been implicated in the assembly of centromeric heterochromatin. Fission yeast cells lacking Abp1 show an increase in mini-chromosome instability suggesting that Abp1 is important for chromosome segregation and/or DNA synthesis. Here we show that Abp1 interacts with the DNA replication protein Cdc23 (MCM10) in a two-hybrid assay, and that the Δabp1 mutant displays a synthetic phenotype with a cdc23 temperature-sensitive mutant. Moreover, genetic interactions were also observed between abp1
+ and four additional DNA replication initiation genes cdc18
+, cdc21
+, orc1
+, and orc2
+. Interestingly, we find that S phase is delayed in cells deleted for abp1
+ when released from a G1 block. However, no delay is observed when cells are released from an early S phase arrest induced by hydroxyurea suggesting that Abp1 functions prior to, or coincident with, the initiation of DNA replication.
Real-time ultrasound-guided catheterisation of the internal jugular vein: a prospective comparison with the landmark technique in critical care patients
Authors: Karakitsos Dimitrios , Labropoulos Nicolaos , De Groot Eric , Patrianakos Alexandros P , Kouraklis Gregorios , Poularas John , Samonis George , Tsoutsos Dimosthenis A , Konstadoulakis Manousos M , Karabinis Andreas 
Published: November 2006

Abstract
Introduction
Central venous cannulation is crucial in the management of the critical care patient. This study was designed to evaluate whether real-time ultrasound-guided cannulation of the internal jugular vein is superior to the standard landmark method.

Methods
In this randomised study, 450 critical care patients who underwent real-time ultrasound-guided cannulation of the internal jugular vein were prospectively compared with 450 critical care patients in whom the landmark technique was used. Randomisation was performed by means of a computer-generated random-numbers table, and patients were stratified with regard to age, gender, and body mass index.

Results
There were no significant differences in gender, age, body mass index, or side of cannulation (left or right) or in the presence of risk factors for difficult venous cannulation such as prior catheterisation, limited sites for access attempts, previous difficulties during catheterisation, previous mechanical complication, known vascular abnormality, untreated coagulopathy, skeletal deformity, and cannulation during cardiac arrest between the two groups of patients. Furthermore, the physicians who performed the procedures had comparable experience in the placement of central venous catheters (p = non-significant). Cannulation of the internal jugular vein was achieved in all patients by using ultrasound and in 425 of the patients (94.4%) by using the landmark technique (p < 0.001). Average access time (skin to vein) and number of attempts were significantly reduced in the ultrasound group of patients compared with the landmark group (p < 0.001). In the landmark group, puncture of the carotid artery occurred in 10.6% of patients, haematoma in 8.4%, haemothorax in 1.7%, pneumothorax in 2.4%, and central venous catheter-associated blood stream infection in 16%, which were all significantly increased compared with the ultrasound group (p < 0.001).

Conclusion
The present data suggest that ultrasound-guided catheterisation of the internal jugular vein in critical care patients is superior to the landmark technique and therefore should be the method of choice in these patients.
Calcitonin gene-related peptide inhibits early B cell development in vivo
Authors: Schlomer Jerome J , Storey Benjamin B , Ciornei Radu-Tudor , McGillis Joseph P 
Published: November 2006

AbstractRecent in vitro studies suggest that calcitonin gene-related peptide (CGRP) inhibits early B cell differentiation; however, there is no evidence in the intact animal for a role for CGRP in B cell development. Here, we show that in vivo treatment of mice with CGRP reduces the number of IL-7 responsive B cell progenitors in bone marrow. A single CGRP treatment reduces IL-7-responsive B cell progenitors by up to 40% for up to 72 h. The reduction is dose-dependent and can be blocked by a CGRP receptor antagonist, CGRP8–37. CGRP in serum following injection is highly elevated at 30 min but returns to basal levels by 4 h, suggesting that a single injection of CGRP has long-lasting effects on B cell development. This report provides the first direct in vivo evidence that CGRP, a neuropeptide with multiple effects on mature lymphocytes, also plays a regulatory role in early B cell development in the bone marrow.
Emergency Medicine Practitioner Knowledge and Use of Decision Rules for the Evaluation of Patients with Suspected Pulmonary Embolism: Variations by Practice Setting and Training Level
Authors: Runyon Michael S. , Richman Peter B. , Kline Jeffrey A. 
Published: November 2006

Abstract Background Several clinical decision rules (CDRs) have been validated for pretest probability assessment of pulmonary embolism (PE), but the authors are unaware of any data quantifying and characterizing their use in emergency departments. Objectives To characterize clinicians' knowledge of and attitudes toward two commonly used CDRs for PE. Methods By using a modified Delphi approach, the authors developed a two‐page paper survey including 15 multiple‐choice questions. The questions were designed to determine the respondents' familiarity, frequency of use, and comprehension of the Canadian and Charlotte rules. The survey also queried the frequency of use of unstructured (gestalt) pretest probability assessment and reasons why physicians choose not to use decision rules. The surveys were sent to physicians, physician assistants, and medical students at 32 academic and community hospitals in the United States and the United Kingdom. Results Respondents included 555 clinicians; 443 (80%) work in academic practice, and 112 (20%) are community based. Significantly more academic practitioners (73%) than community practitioners (49%) indicated familiarity with at least one of the two decision rules. Among all respondents familiar with a rule, 50% reported using it in more than half of applicable cases. A significant number of these respondents could not correctly identify a key component of the rule (23% for the Charlotte rule and 43% for the Canadian rule). Fifty‐seven percent of all respondents indicated use of gestalt rather than a decision rule in more than half of cases. Conclusions Academic clinicians were more likely to report familiarity with either of these two specific decision rules. Only one half of all clinicians reporting familiarity with the rules use them in more than 50% of applicable cases. Spontaneous recall of the specific elements of the rules was low to moderate. Future work should consider clinical gestalt in the evaluation of patients with possible PE.
Factors Associated with Hospital Admission among Emergency Department Patients with Chronic Obstructive Pulmonary Disease Exacerbation
Authors: Tsai Chu‐Lin , Clark Sunday , Cydulka Rita K. , Rowe Brian H. , Camargo Carlos A. 
Published: November 2006

Abstract Objectives To determine the patient factors associated with hospital admission among adults who present to the emergency department (ED) with acute exacerbations of chronic obstructive pulmonary disease (COPD) and to determine whether admissions were concordant with recommendations in the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines. Methods The authors performed a prospective multicenter cohort study involving 29 EDs in the United States and Canada. By using a standard protocol, consecutive ED patients with COPD exacerbation were interviewed, and their charts were reviewed. Predictors of admission were determined by multivariate logistic regression. Results Of 384 patients, 233 (61%; 95% confidence interval = 56% to 66%) were admitted. Multivariate analysis showed that a higher likelihood of admission was associated with older age, female gender, more pack‐years of smoking, recent use of inhaled corticosteroid, self‐reported activity limitation in the past 24 hours, higher respiratory rate at ED presentation, and a concomitant diagnosis of pneumonia. Patients who reported the ED as their usual site for problem COPD care, or who had mixed COPD and asthma, were less likely to be admitted. The authors confirmed five of the seven testable indications for hospital admission in the GOLD guidelines. Conclusions Several patient factors were independently associated with hospital admission among ED patients with COPD exacerbations. Overall, concordance with admission recommendations in the GOLD guidelines was high. The authors also identified a few novel predictors of admission (female gender, ED as the usual site for problem COPD care, mixed diagnosis of COPD and asthma, recent use of inhaled corticosteroid) that require replication in future studies.
Morphology and action of the hind leg joints controlling jumping in froghopper insects
Authors: Burrows Malcolm 
Published: November 2006

SUMMARYThe morphology and movements of key joints of the hind legs that generate the rapid jumping of froghoppers were analysed. The movements of an individual hind leg during a jump occur in three phases. First, the trochanter is slowly levated about the coxa so that the femur moves anteriorly and engages with a lateral protrusion on the coxa. Second, both hind legs are held in this fully levated (cocked) position without moving for a few seconds. Third, both hind legs depress and extend completely in less than 1 ms. The critical,power-generating movement underlying a jump is the rapid and simultaneous depression of the trochantera about the coxae.The lever arm of the hind trochanteral depressor muscle is smallest at the cocked position, but does not appear to go over the centre of the pivot. It then increases to a maximum after some 80° of depression movement. By contrast, the lever arm of the trochanteral levator tendon is similar over the range of joint movements and is exceeded by that of the depressor only after 40° of depression. Three prominent arrays of hairs on the trochantin, coxa and trochanter are appropriately positioned to act as proprioceptors signalling key movements in jumping.In the fully levated position, a protrusion on the dorsal, proximal surface of a hind femur engages with a protrusion from the ventral and lateral part of a coxa. These structures are not present on the front and middle legs. Both protrusions are covered with a dense array of small projections (microtrichia)that both increase the surface area and may interlock with each other. To depress rapidly in a jump these protrusions must disengage. If the hind leg of a dead froghopper is forcibly levated, it will lock in its cocked position,from which it can depress rapidly by movement of the coxo-trochanteral joint and disengagement of the femoral and coxal protrusions. A prominent click sound occurs at the start of a jump that results either from the initial movements of the coxo-trochanteral joint, or from the disengagement of the microtrichia on the coxa and femur. Larval Philaenus, which do not jump, lack a femoral protrusion and have no microtrichia in equivalent positions on either the coxa or femur.