bluuebunny/crossref_metadata_2025_split huggingface dataset:
The inositol phosphatase SHIP-1 is negatively regulated by Fli-1 and its loss accelerates leukemogenesis
Authors: Lakhanpal Gurpreet K. , Vecchiarelli-Federico Laura M. , Li You-Jun , Cui Jiu-Wei , Bailey Monica L. , Spaner David E. , Dumont Daniel J. , Barber Dwayne L. , Ben-David Yaacov 
Published: May 2010

AbstractThe activation of Fli-1, an Ets transcription factor, is the critical genetic event in Friend murine leukemia virus (F-MuLV)–induced erythroleukemia. Fli-1 overexpression leads to erythropoietin-dependent erythroblast proliferation, enhanced survival, and inhibition of terminal differentiation, through activation of the Ras pathway. However, the mechanism by which Fli-1 activates this signal transduction pathway has yet to be identified. Down-regulation of the Src homology 2 (SH2) domain-containing inositol-5-phosphatase-1 (SHIP-1) is associated with erythropoietin-stimulated erythroleukemic cells and correlates with increased proliferation of transformed cells. In this study, we have shown that F-MuLV–infected SHIP-1 knockout mice display accelerated erythroleukemia progression. In addition, RNA interference (RNAi)-mediated suppression of SHIP-1 in erythroleukemia cells activates the phosphatidylinositol 3-kinase (PI 3-K) and extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) pathways, blocks erythroid differentiation, accelerates erythropoietin-induced proliferation, and leads to PI 3-K–dependent Fli-1 up-regulation. Chromatin immunoprecipitation and luciferase assays confirmed that Fli-1 binds directly to an Ets DNA binding site within the SHIP-1 promoter and suppresses SHIP-1 transcription. These data provide evidence to suggest that SHIP-1 is a direct Fli-1 target, SHIP-1 and Fli-1 regulate each other in a negative feedback loop, and the suppression of SHIP-1 by Fli-1 plays an important role in the transformation of erythroid progenitors by F-MuLV.
Bioinformatic prediction, deep sequencing of microRNAs and expression analysis during phenotypic plasticity in the pea aphid, Acyrthosiphon pisum
Authors: Legeai Fabrice , Rizk Guillaume , Walsh Thomas , Edwards Owain , Gordon Karl , Lavenier Dominique , Leterme Nathalie , Méreau Agnès , Nicolas Jacques , Tagu Denis , Jaubert-Possamai Stéphanie 
Published: May 2010

Abstract

Background
Post-transcriptional regulation in eukaryotes can be operated through microRNA (miRNAs) mediated gene silencing. MiRNAs are small (18-25 nucleotides) non-coding RNAs that play crucial role in regulation of gene expression in eukaryotes. In insects, miRNAs have been shown to be involved in multiple mechanisms such as embryonic development, tissue differentiation, metamorphosis or circadian rhythm. Insect miRNAs have been identified in different species belonging to five orders: Coleoptera, Diptera, Hymenoptera, Lepidoptera and Orthoptera.

Results
We developed high throughput Solexa sequencing and bioinformatic analyses of the genome of the pea aphid Acyrthosiphon pisum in order to identify the first miRNAs from a hemipteran insect. By combining these methods we identified 149 miRNAs including 55 conserved and 94 new miRNAs. Moreover, we investigated the regulation of these miRNAs in different alternative morphs of the pea aphid by analysing the expression of miRNAs across the switch of reproduction mode. Pea aphid microRNA sequences have been posted to miRBase: http://microrna.sanger.ac.uk/sequences/

Conclusions
Our study has identified candidates as putative regulators involved in reproductive polyphenism in aphids and opens new avenues for further functional analyses.
Prognostic utility of chromosomal instability detected by fluorescence in situ hybridization in fine-needle aspirates from oral squamous cell carcinomas
Authors: Sato Hiroaki , Uzawa Narikazu , Takahashi Ken-Ichiro , Myo Kunihiro , Ohyama Yoshio , Amagasa Teruo 
Published: May 2010

Abstract

Background
Although chromosomal instability (CIN) has been detected in many kinds of human malignancies by means of various methods, there is no practical assessment for small clinical specimens. In this study, we evaluated CIN in fine-needle aspiration (FNA) biopsied oral squamous cell carcinomas (SCCs) using fluorescence in situ hybridization (FISH) analysis, and investigated its prognostic significance.

Methods
To evaluate CIN status of tumors, FISH with genomic probes for the centromeres of chromosomes 7, 9, and 11 was performed on specimens obtained by FNA from 77 patients with primary oral SCCs.

Results
High-grade CIN (CIN3) was observed in 11.7% (9/77) of patients with oral SCCs and was associated significantly with reduced disease-free survival (p = .008) and overall survival (p = .003). Multivariate Cox proportional hazards analysis showed that CIN status was significantly correlated with disease-free survival (p = .035) and overall survival (p = .041).

Conclusion
Analysis of CIN status using FISH on FNA biopsy specimens may be useful in predicting of recurrence and poor prognosis in patients with oral SCCs.
Distinct high resolution genome profiles of early onset and late onset colorectal cancer integrated with gene expression data identify candidate susceptibility loci
Authors: Berg Marianne , Ågesen Trude H , Thiis-Evensen Espen ,   [the INFAC-study group], Merok Marianne A , Teixeira Manuel R , Vatn Morten H , Nesbakken Arild , Skotheim Rolf I , Lothe Ragnhild A 
Published: May 2010

Abstract

Background
Estimates suggest that up to 30% of colorectal cancers (CRC) may develop due to an increased genetic risk. The mean age at diagnosis for CRC is about 70 years. Time of disease onset 20 years younger than the mean age is assumed to be indicative of genetic susceptibility. We have compared high resolution tumor genome copy number variation (CNV) (Roche NimbleGen, 385 000 oligo CGH array) in microsatellite stable (MSS) tumors from two age groups, including 23 young at onset patients without known hereditary syndromes and with a median age of 44 years (range: 28-53) and 17 elderly patients with median age 79 years (range: 69-87). Our aim was to identify differences in the tumor genomes between these groups and pinpoint potential susceptibility loci. Integration analysis of CNV and genome wide mRNA expression data, available for the same tumors, was performed to identify a restricted candidate gene list.

Results
The total fraction of the genome with aberrant copy number, the overall genomic profile and the TP53 mutation spectrum were similar between the two age groups. However, both the number of chromosomal aberrations and the number of breakpoints differed significantly between the groups. Gains of 2q35, 10q21.3-22.1, 10q22.3 and 19q13.2-13.31 and losses from 1p31.3, 1q21.1, 2q21.2, 4p16.1-q28.3, 10p11.1 and 19p12, positions that in total contain more than 500 genes, were found significantly more often in the early onset group as compared to the late onset group. Integration analysis revealed a covariation of DNA copy number at these sites and mRNA expression for 107 of the genes. Seven of these genes, CLC, EIF4E, LTBP4, PLA2G12A, PPAT, RG9MTD2, and ZNF574, had significantly different mRNA expression comparing median expression levels across the transcriptome between the two groups.

Conclusions
Ten genomic loci, containing more than 500 protein coding genes, are identified as more often altered in tumors from early onset versus late onset CRC. Integration of genome and transcriptome data identifies seven novel candidate genes with the potential to identify an increased risk for CRC.
A study on the applicability of implantable microchip transponders for body temperature measurements in pigs
Authors: Lohse Louise , Uttenthal Åse , Enøe Claes , Nielsen Jens 
Published: May 2010

Abstract

Background
The applicability of an electronic monitoring system using microchip transponders for measurement of body temperatures was tested in 6-week-old conventional Danish weaners infected with classical swine fever virus (CSFV). Subcutaneous tissue temperatures obtained by the implantable transponders were compared with rectal temperatures, recorded by a conventional digital thermometer.

Methods
In a preliminary study, transponders were inserted subcutaneously at 6 different positions of the body of 5 pigs. The transponders positioned by the ear base provided the best correlation to rectal temperature. To test the stability of the monitoring system in a larger group of pigs, transponders were therefore inserted by the left ear base in a subsequent infection experiment with 30 pigs.

Results
Generally, the microchip transponders measured a subcutaneous tissue temperature, which was about 1°C lower than the rectal temperature. However, a simple linear relationship between the measures of the two methods was found.

Conclusions
Our study showed that the tested body monitoring system may represent a promising tool to obtain an approximate correlate of body temperatures in groups of pigs. In contrast, however, the tested system did not constitute a suitable tool to measure body temperatures of individual animals in the present pig infection experiment.
Seven-year follow-up of infliximab therapy in rheumatoid arthritis patients with severe long-standing refractory disease: attrition rate and evolution of disease activity
Authors: Vander Cruyssen Bert , Durez Patrick , Westhovens Rene , De Keyser Filip 
Published: May 2010

Abstract
Introduction
This study is based on the results from a Belgian expanded access program in which patients with active refractory and erosive rheumatoid arthritis (RA) were treated with intravenous infusions of infliximab in combination with methotrexate. The objectives of this study were to evaluate the continuation rate of infliximab and its clinical effect over a 7-year period and to document the reasons for discontinuation.

Methods
Between 2000 and 2001, 511 patients with severe and refractory RA were enrolled and treated with infliximab. After 7 years, apart from routine clinical follow-up, treating rheumatologists were asked to complete a questionnaire designed specifically for the present study to evaluate the current therapy with infliximab, the level of disease activity (Disease Activity Score in 28 joints [DAS28]) and the reasons for infliximab discontinuation.

Results
After 7 years, 160 of 511 patients (31%) were still on infliximab treatment. The major reasons for infliximab discontinuation included lack of efficacy (104 patients), adverse events (107 patients) and elective change of therapy (70 patients). The majority of cases of treatment discontinuation for safety reasons occurred during the first 2 years. In contrast, discontinuation due to ineffectiveness showed a more constant rate over the 7-year period. Mean DAS for patients still on treatment with infliximab decreased from 5.7 (standard error [SE] 0.1) at baseline to 3.0 (SE 0.1) at year 4 and remained that low until year 7 (3.0 [SE 0.1]). Low disease activity (defined as DAS28 <3.2) was present in 60.9% of patients, and 45.5% achieved remission (DAS28 <2.6). DAS28 at the time of treatment discontinuation due to ineffectiveness decreased over the 7-year period from 5.6 (SE 0.3) in 2001 to 4.8 (SE 0.3) in 2008.

Conclusions
This observational study revealed that patients who continue to receive infliximab experience sustained clinical benefit. The majority of safety issues occurred during the first 2 years of infliximab therapy. We observed that the DAS at the time of therapy discontinuation showed a trend to decrease over time.
Endothelial cell markers reflecting endothelial cell dysfunction in patients with mixed connective tissue disease
Authors: Soltesz Pal , Bereczki Daniel , Szodoray Peter , Magyar Maria T , Der Henrietta , Csipo Istvan , Hajas Agota , Paragh Gyorgy , Szegedi Gyula , Bodolay Edit 
Published: May 2010

Abstract
Introduction
The aim of the present study was to investigate the association between cardiovascular risk factors and endothelial dysfunction in patients with mixed connective tissue disease (MCTD) and to determine which biomarkers are associated with atherosclerotic complications, such as cardiovascular disease.

Methods
Fifty MCTD patients and 38 healthy age-matched and sex-matched controls were enrolled in this study. In order to describe endothelial dysfunction, we assessed flow-mediated dilation (FMD), nitrate-mediated dilation (NMD) and carotid artery intima-media thickness (IMT). We investigated FMD of the brachial artery after reactive hyperemia and NMD after sublingual nitroglycerin administration, while the IMT of the common carotid artery was determined by ultrasound. Anti-U1 ribonucleoprotein (anti-U1RNP) antibodies, anti-cardiolipin (anti-CL) antibodies, anti-endothelial cell antibody (AECA) and endothelial cell markers, such as soluble thrombomodulin (TM) and von Willebrand factor antigen (vWFAg), were assessed.

Results
The endothelium-dependent vasodilation (FMD) was significantly impaired in patients with MCTD, as compared with controls (%FMD: 4.7 ± 4.2% vs. 8.7 ± 5.0%; P < 0.001), while the percentage NMD did not differ (%NMD: 14.3 ± 6.6% vs. 17.1 ± 6.7%; P = 0.073). Mean carotid IMT values were higher in patients than in controls (IMT: MCTD, 0.64 ± 0.13 mm vs. controls, 0.53 ± 0.14 mm; P < 0.001). FMD negatively correlated with disease duration, the levels of apolipoprotein A1, the paraoxonase-1 activity, and systolic blood pressure in MCTD patients. The percentage FMD was significantly lower in MCTD patients with cardiovascular diseases (CVD), than in those without CVD (%FMD: 3.5 ± 2.9 vs. 5.8 ± 4.8, P < 0.0002), while percentage NMD did not differ between patients with and without CVDs. Serum levels of autoantibodies (anti-U1RNP, AECA and anti-CL) were significantly higher in MCTD patients and differed between MCTD patients with and without CVD. Endothelial cell markers such as soluble TM (12.2 ± 8.1 ng/ml vs. 3.2 ± 1.3 ng/ml; P < 0.001) and vWFAg (224.1 ± 115% vs. 89.4 ± 27.1%, P < 0.001) were the highest in MCTD patients with CVD.

Conclusions
FMD is a reliable sensitive marker of endothelial cell dysfunction in MCTD. Beside the traditional risk factors, anti-U1RNP, AECA and anti-CL antibodies may be important not only in the pathogenesis of MCTD but in the induction of endothelial cell activation, and may play crucial roles in the development of early atherosclerosis in MCTD.
Ethnic Differences in Insulin Action in Obese African-American and Latino Adolescents
Authors: Hasson Rebecca E. , Adam Tanja C. , Davis Jaimie N. , Weigensberg Marc J. , Ventura Emily E. , Lane Christianne J. , Roberts Christian K. , Goran Michael I. 
Published: May 2010

Introduction: African-American children have a greater acute insulin response to iv glucose (AIR) compared with Latino children despite a similar degree of insulin resistance and body composition. It is unclear whether African-Americans demonstrate an exaggerated insulin response to an oral glucose challenge and whether any differences are seen in more obese children in advanced pubertal development.
Purpose: Our objective was to compare glucose and insulin indices derived from an oral glucose tolerance test (OGTT) and iv glucose tolerance test (IVGTT) in sedentary, obese African-American (n = 59) and Latino (n = 83) adolescents.
Methods: Glucose and insulin incremental area under the curve was measured during an OGTT, and AIR, insulin sensitivity, disposition index, and glucose effectiveness were assessed during an IVGTT. Body composition was assessed via dual-energy x-ray absorptiometry and magnetic resonance imaging.
Results: From the OGTT, glucose and insulin IAUC were 29.1 and 22.5% lower (P = 0.01) in African-Americans compared with Latino adolescents. From the IVGTT, insulin sensitivity and glucose effectiveness were 41.7% (P &lt; 0.01) and 50.0% (P = 0.02) lower in African-Americans compared to Latinos. AIR (P = 0.001) and disposition index (P = 0.02) were 63.0 and 48.8% higher in African-Americans, respectively, compared with Latinos. These findings persisted after controlling for body composition and fat distribution.
Conclusions: There were marked differences in glucose and insulin indices derived from the OGTT and IVGTT. African-Americans were more insulin resistant as measured by the IVGTT compared with the Latino adolescents. However, the well-described hyperinsulinemia in response to iv glucose was not observed after oral glucose in African-American adolescents.
Inhibition of Protein Kinase Cβ Does Not Improve Endothelial Function in Type 2 Diabetes
Authors: Beckman Joshua A. , Goldfine Allison B. , Goldin Alison , Prsic Adnan , Kim Sora , Creager Mark A. 
Published: May 2010

Context: Antagonism of protein kinase Cβ (PKCβ) restores endothelial function in experimental models of diabetes and prevents vascular dysfunction in response to hyperglycemia in healthy humans.
Objective: We tested the hypothesis that PKCβ antagonism would improve vascular function in subjects with type 2 diabetes compared with healthy control subjects.
Design: The effect of PKCβ was evaluated in a randomized, placebo-controlled, double-blinded crossover trial.
Setting: The study was performed in the outpatient setting of a university medical center.
Participants: Thirteen subjects with type 2 diabetes without evidence of cardiovascular disease and 15 healthy control subjects were recruited via newspaper advertisement.
Intervention: Subjects underwent a randomized, double-blind, crossover, placebo-controlled trial of the selective PKCβ antagonist ruboxistaurin mesylate. Subjects received each treatment for 14 d.
Main Outcome Measure: Endothelium-dependent and endothelium-independent vasodilation of forearm resistance vessels was measured with mercury-in-silastic, strain-gauge plethysmography during intraarterial administration of methacholine chloride and verapamil, respectively. Markers of inflammation, fibrinolysis, endothelial damage, and oxidative stress were measured after each treatment.
Results: Endothelium-dependent vasodilation of forearm resistance vessels was attenuated in diabetic subjects when compared with healthy subjects (P = 0.001). Endothelium-independent vasodilation did not differ between groups (P value not significant). Ruboxistaurin did not significantly change endothelium-dependent or endothelium-independent vasodilation or blood-based markers of inflammation, fibrinolysis, endothelial damage, and oxidative stress in either diabetic or healthy subjects.
Conclusion: Endothelial dysfunction of forearm resistance vessels was not improved by 2 wk of selective PKCβ inhibition in patients with diabetes. These results suggest that PKCβ does not contribute significantly to vascular dysfunction in otherwise healthy patients with type 2 diabetes.
Abstinence and Teenagers: Prevention Counseling Practices of Health Care Providers Serving High‐Risk Patients in the United States
Authors: Harper Cynthia C. , Henderson Jillian T. , Schalet Amy , Becker Davida , Stratton Laura , Raine Tina R. 
Published: May 2010

CONTEXT: Abstinence‐only education has had little demonstrable impact on teenagers' sexual behaviors, despite significant policy and funding efforts. Given the struggle over resources to improve teenagers' reproductive health outcomes, the views of clinicians serving teenagers at high risk for unintended pregnancy and STDs merit particular attention.
METHODS: In 2005, a qualitative study with 31 clinicians serving low‐income, at‐risk patients was conducted. A semistructured interview guide was used to ask clinicians about adolescent pregnancy, HIV and STD prevention counseling, and when they include abstinence. Thematic content analysis was used to examine the content of the counseling and the techniques used in different situations.
RESULTS: Providers reported offering comprehensive counseling, presenting abstinence as a choice for teenagers, along with information about contraceptives and condoms. Several providers mentioned that with young, sexually inexperienced teenagers, they discuss delaying sexual activity and suggest other ways to be affectionate, while giving information on condoms. Providers explained how they assess whether teenagers feel ready to be sexually active and try to impart skills for healthy relationships. Some described abstinence as giving teenagers a way to opt out of unwanted sexual activity. Many support abstinence if that is the patient's desire, but routinely dispense condoms and contraceptives.
CONCLUSIONS: Overall, providers did not give abstinence counseling as a rigid categorical concept in their preventive practices, but as a health tool to give agency to teenagers within a harm reduction framework. Their approach may be informative for adolescent policies and programs in the future.
Contribution of flow cytometry to the diagnosis and differential diagnosis of thrombocytopenia1
Authors: Mauerer Richard , Gruber Rudolf 
Published: May 2010

Abstract
Thrombocytopenia is commonly found in patients with apparent bleeding tendency, and in the laboratory evaluation of patients with other disorders or in clinically healthy individuals. Identification of the underlying cause is therefore crucial. There are several different laboratory tests available for this purpose. Flow cytometry employs very small sample volumes, which is of particular interest in patients with severe thrombocytopenia or in pediatric samples. Thus, the immunological determination of platelet numbers by flow cytometry is recommended as the reference method to achieve an exact quantification of very low platelet numbers, which could influence therapeutic decisions. In addition, flow cytometric analysis of immature platelets plays a role in the differentiation of increased platelet destruction and decreased platelet synthesis. As this parameter can be measured by current hematology analyzers, it will become more important in routine use. Another field for flow cytometry is the investigation of immunologically mediated thrombocytopenias. These can be caused by antibodies against platelet-specific glycoproteins such as autoimmune thrombocytopenia or by antibodies against heparin-platelet factor 4 complexes such as heparin-induced thrombocytopenia. Moreover, flow cytometric assays are used for the diagnosis of rare congenital thrombocytopenias, where they are either able to confirm a certain diagnosis, e.g., Bernard-Soulier syndrome, or at least establish a basis for further analyses. The contribution of flow cytometry to the investigation of lymphoma and leukemia, which regularly cause thrombocytopenia by bone marrow infiltration, is not discussed in this article.
Das Adverb jetzt zwischen Zeit- und Gesprächsdeixis
Authors: Imo Wolfgang 
Published: May 2010

Abstract
The adverb jetzt is used extremely frequently in everyday spoken language. Usually, jetzt is described as a deictic adverb which activates a concept of temporal proximity (“now”), which is contrasted to some past or future temporal distance (“not now”). Indeed, one can find many instances of such a basic temporal use of jetzt in data of spoken German. Often, however, the functions of jetzt are somewhat more complicated: Sometimes, jetzt is used to refer back in time, in other cases it refers forward, in yet other instances, it refers to some virtual temporal and discourse-structural space within narratives, sometimes, it is a semantically empty discourse marker which is used to structure and partition talk, and finally, there are cases where jetzt can only be described in terms of a conglomerate of several of these meanings and functions. On the basis of a corpus of spoken German (including audio material from the second series of the TV show Big Brother, radio phone-in shows and informal interaction between friends or families) this article aims to give a qualitative and detailed description of the syntactic, prosodic, semantic, functional and sequential features of the different uses of jetzt within this corpus. In a next step, the question is asked which of these features are necessary and sufficient for a full description and finally, an attempt is made to integrate these findings into the descriptive framework of Construction Grammar.