bluuebunny/crossref_metadata_2025_split huggingface dataset:
STAT3 controls myeloid progenitor growth during emergency granulopoiesis
Authors: Zhang Huiyuan , Nguyen-Jackson Hoainam , Panopoulos Athanasia D. , Li Haiyan S. , Murray Peter J. , Watowich Stephanie S. 
Published: June 2010

AbstractGranulocyte colony-stimulating factor (G-CSF) mediates “emergency” granulopoiesis during infection, a process that is mimicked by clinical G-CSF use, yet we understand little about the intracellular signaling cascades that control demand-driven neutrophil production. Using a murine model with conditional deletion of signal transducer and activator of transcription 3 (STAT3) in bone marrow, we investigated the cellular and molecular mechanisms of STAT3 function in the emergency granulopoiesis response to G-CSF administration or infection with Listeria monocytogenes, a pathogen that is restrained by G-CSF signaling in vivo. Our results show that STAT3 deficiency renders hematopoietic progenitor cells and myeloid precursors refractory to the growth-promoting functions of G-CSF or L monocytogenes infection. STAT3 is necessary for accelerating granulocyte cell-cycle progression and maturation in response to G-CSF. STAT3 directly controls G-CSF–dependent expression of CCAAT-enhancer-binding protein β (C/EBPβ), a crucial factor in the emergency granulopoiesis response. Moreover, STAT3 and C/EBPβ coregulate c-Myc through interactions with the c-myc promoter that control the duration of C/EBPα occupancy during demand-driven granulopoiesis. These results place STAT3 as an essential mediator of emergency granulopoiesis by its regulation of transcription factors that direct G-CSF–responsive myeloid progenitor expansion.
Multilineage dysplasia (MLD) in acute myeloid leukemia (AML) correlates with MDS-related cytogenetic abnormalities and a prior history of MDS or MDS/MPN but has no independent prognostic relevance: a comparison of 408 cases classified as “AML not otherwise specified” (AML-NOS) or “AML with myelodysplasia-related changes” (AML-MRC)
Authors: Miesner Miriam , Haferlach Claudia , Bacher Ulrike , Weiss Tamara , Macijewski Katja , Kohlmann Alexander , Klein Hans-Ulrich , Dugas Martin , Kern Wolfgang , Schnittger Susanne , Haferlach Torsten 
Published: June 2010

Abstract
The World Health Organization classification of acute myeloid leukemia (AML) is hierarchically structured and integrates genetics, data on patients' history, and multilineage dysplasia (MLD). The category “AML with myelodysplastic syndrome (MDS)–related changes” (AML-MRC) is separated from “AML not otherwise specified” (AML-NOS) by presence of MLD, MDS-related cytogenetics, or history of MDS or MDS/myeloproliferative neoplasm (MPN). We analyzed 408 adult patients categorized as AML-MRC or AML-NOS. Three-year event-free survival (EFS; median, 13.8 vs 16.0 months) and 3-year overall survival (OS; 45.8% vs 53.9%) did not differ significantly between patients with MLD versus without. However, MLD correlated with preexisting MDS (P < .001) and MDS-related cytogenetics (P = .035). Patients with MLD as sole AML-MRC criterion (AML-MLD-sole; n = 90) had less frequently FLT3 internal tandem duplication (P = .032) and lower median age than AML-NOS (n = 232). Contrarily, patients with AML-NOS combined with AML-MLD-sole (n = 323) had better 3-year EFS (16.9 vs 10.7 months; P = .005) and 3-year OS (55.8% vs 32.5%; P = .001) than patients with history of MDS or MDS/MPN or MDS-related cytogenetics (n = 85). Gene expression analysis showed distinct clusters for AML-MLD-sole combined with AML-NOS versus AML with MDS-related cytogenetics or MDS history. Thus, MLD alone showed no independent clinical effect, whereas cytogenetics and MDS history were prognostically relevant.
Donor selection for natural killer cell receptor genes leads to superior survival after unrelated transplantation for acute myelogenous leukemia
Authors: Cooley Sarah , Weisdorf Daniel J. , Guethlein Lisbeth A. , Klein John P. , Wang Tao , Le Chap T. , Marsh Steven G. E. , Geraghty Daniel , Spellman Stephen , Haagenson Michael D. , Ladner Martha , Trachtenberg Elizabeth , Parham Peter , Miller Jeffrey S. 
Published: June 2010

AbstractKiller-cell immunoglobulin-like receptor (KIR) genes form a diverse, immunogenetic system. Group A and B KIR haplotypes have distinctive centromeric (Cen) and telomeric (Tel) gene-content motifs. Aiming to develop a donor selection strategy to improve transplant outcome, we compared the contribution of these motifs to the clinical benefit conferred by B haplotype donors. We KIR genotyped donors from 1409 unrelated transplants for acute myelogenous leukemia (AML; n = 1086) and acute lymphoblastic leukemia (ALL; n = 323). Donor KIR genotype influenced transplantation outcome for AML but not ALL. Compared with A haplotype motifs, centromeric and telomeric B motifs both contributed to relapse protection and improved survival, but Cen-B homozygosity had the strongest independent effect. With Cen-B/B homozygous donors the cumulative incidence of relapse was 15.4% compared with 36.5% for Cen-A/A donors (relative risk of relapse 0.34; 95% confidence interval 0.2-0.57; P < .001). Overall, significantly reduced relapse was achieved with donors having 2 or more B gene-content motifs (relative risk 0.64; 95% confidence interval 0.48-0.86; P = .003) for both HLA-matched and mismatched transplants. KIR genotyping of several best HLA-matched potential unrelated donors should substantially increase the frequency of transplants by using grafts with favorable KIR gene content. Adopting this practice could result in superior disease-free survival for patients with AML.
The CS1 segment of fibronectin is involved in human OSCC pathogenesis by mediating OSCC cell spreading, migration, and invasion
Authors: Kamarajan Pachiyappan , Garcia-Pardo Angeles , D'Silva Nisha J , Kapila Yvonne L 
Published: June 2010

Abstract

Background
The alternatively spliced V region or type III connecting segment III (IIICS) of fibronectin is important in early development, wound healing, and tumorigenesis, however, its role in oral cancer has not been fully investigated. Thus, we investigated the role of CS-1, a key site within the CSIII region of fibronectin, in human oral squamous cell carcinoma (OSCC).

Methods
To determine the expression of CS-1 in human normal and oral SCC tissue specimens immunohistochemical analyses were performed. The expression of CS1 was then associated with clinicopathological factors. To investigate the role of CS-1 in regulating OSCC cell spreading, migration and invasion, OSCC cells were assayed for spreading and migration in the presence of a CS-1 peptide or a CS-1 blocking peptide, and for invasion using Matrigel supplemented with these peptides. In addition, integrin α4siRNA or a focal adhesion kinase (FAK) anti-sense oligonucleotide was transfected into OSCC cells to examine the mechanistic role of integrin α4 or FAK in CS1-mediated cell spreading and migration, respectively.

Results
CS-1 expression levels were significantly higher in OSCC tissues compared to normal tissues (p < 0.05). Also, although, high levels of CS-1 expression were present in all OSCC tissue samples, low-grade tumors stained more intensely than high grade tumors. OSCC cell lines also expressed higher levels of CS-1 protein compared to normal human primary oral keratinocytes. There was no significant difference in total fibronectin expression between normal and OSCC tissues and cells. Inclusion of CS-1 in the in vitro assays enhanced OSCC cell spreading, migration and invasion, whereas the CS1 blocking peptide inhibited these processes. Suppression of integrin α4 significantly inhibited the CS1-mediated cell spreading. Furthermore, this migration was mediated by focal adhesion kinase (FAK), since FAK suppression significantly blocked the CS1-induced cell migration.

Conclusion
These data indicate that the CS-1 site of fibronectin is involved in oral cancer pathogenesis and in regulating OSCC cell spreading, migration and invasion.
EGFR isoforms and gene regulation in human endometrial cancer cells
Authors: Albitar Lina , Pickett Gavin , Morgan Marilee , Wilken Jason A , Maihle Nita J , Leslie Kimberly K 
Published: June 2010

AbstractBackgroundEpidermal growth factor (EGF) and its receptor (EGFR) constitute a principal growth-promoting pathway in endometrial cancer cells. Pre-clinical studies were undertaken to compare the expression of EGFR isoforms and the downstream effects of activating or blocking EGFR function in Ishikawa H cells, derived from a moderately differentiated type I endometrioid adenocarcinoma, or in Hec50co cells, derived from a poorly differentiated type II adenocarcinoma with papillary serous sub-differentiation.ResultsWe investigated whether EGFR mutations are present in the tyrosine kinase domain (exons 18-22) of EGFR and also whether EGFR isoforms are expressed in the Ishikawa H or Hec50co cell lines. Sequence of the EGFR tyrosine kinase domain proved to be wild type in both cell lines. While both cell lines expressed full-length EGFR (isoform A), EGFR and sEGFR (isoform D) were expressed at significantly lower levels in Hec50co cells compared to Ishikawa H cells. Analysis of gene expression following EGF vs. gefitinib treatment (a small molecule EGFR tyrosine kinase inhibitor) was performed. Early growth response 1, sphingosine kinase 2, dual specificity phosphatase 6, and glucocorticoid receptor DNA binding factor 1 are members of a cluster of genes downstream of EGFR that are differentially regulated by treatment with EGF compared to gefitinib in Ishikawa H cells, but not in Hec50co cells.ConclusionsType I Ishikawa H and type II Hec50co endometrial carcinoma cells both express EGFR and sEGFR, but differ markedly in their responsiveness to the EGFR inhibitor gefitinib. This difference is paralleled by differences in the expression of sEGFR and EGFR, as well as in their transcriptional response following treatment with either EGF or gefitinib. The small cluster of differently regulated genes reported here in these type I vs. type II endometrial cancer-derived cell lines may identify candidate biomarkers useful for predicting sensitivity to EGFR blockade.
Prevalence of chronic complications of type 2 diabetes mellitus in outpatients - a cross-sectional hospital based survey in urban China
Authors: Liu Zhaolan , Fu Chaowei , Wang Weibing , Xu Biao 
Published: June 2010

Abstract

Background
Chronic complications are the major outcome of type 2 diabetes mellitus progress, which reduce the quality of life of patients, incur heavy burdens to the health care system, and increase diabetic mortality. The aims of this study were to describe the prevalence of chronic complications among urban Chinese type 2 diabetic outpatients; and to analyze the associations between chronic complications and patients' demographics, diabetic related clinical characteristics.

Methods
This cross-sectional hospital-based study was carried out in 4 major Chinese cities: - Shanghai, Chengdu, Beijing and Guangzhou. The survey was conducted from March to July in 2007 among 1,524 type 2 diabetic outpatients. The subjects were interviewed face-to-face by trained interviewers using a questionnaire to capture information on demographics, disease presentations and complications. All the subjects were invited to have a HbA1c test free of charge by the standardized method with Bio-Rad Variant II.

Results
Of the 1,524 study subjects, 637 (41.8%) were male, and the mean age was 63.3 ± 10.2 years. At least one chronic complication was diagnosed in 792 individuals (52.0%) of the study subjects; 509 (33.4%) presented with macrovascular complications and 528 (34.7%) with microvascular complications. The prevalence of cardiovascular and cerebrovascular conditions, neuropathy, nephropathy, ocular lesions and foot disease were 30.1%, 6.8%, 17.8%, 10.7%, 14.8% and 0.8%, respectively. The prevalence of chronic complications varied between cities, and significantly increased with age and duration of diagnosed diabetes. The mean of HbA1c in diabetic patients with chronic complications was 8.2% ± 1.6% and 63.0% of the subjects with type 2 diabetes related complications had a poor glycemic control with the HbA1c > 7.5%.

Conclusions
Chronic complications are highly prevalent among type 2 diabetic outpatients, the glycemic control of diabetic patients with chronic complications was poor, and future efforts should be directed at intensive blood glucose control, strengthening early diagnosis and improving case management to prevent and minimize the occurrence of complications.
Using a Caesarean Section Classification System based on characteristics of the population as a way of monitoring obstetric practice
Authors: Costa Maria L , Cecatti Jose G , Souza João P , Milanez Helaine M , Gülmezoglu Metin A 
Published: June 2010

AbstractObjectiveto compare the distribution of caesarean rates in the Robson's 10 groups classification in order to see if any change occurred after the implementation of an audit and feedback intervention.Design:cross sectional, before and after an audit and feedback study.Setting: a university hospital in Brazil.Methodsclinical records of all births during two three months-periods were evaluated. Each case of CS was classified into one of ten mutually exclusive categories according to obstetric characteristics. The proportion of CS in each group was compared in both periods.Resultstotal number of deliveries and the high rate of CS were similar in both periods. Group 3 (multiparous excluding previous CS, single, cephalic, ≥ 37 weeks, spontaneous labour) accounted for the largest proportion of deliveries, 28.5 and 26.8% in both periods. Group 1 (nulliparous, single, cephalic, ≥ 37 weeks, spontaneous labour) was the second largest one, while Group 5 (previous caesarean section, single, cephalic, and ≥ 37 weeks) was the third but the largest contributor to CS, accounting for 16.6 and 14.9% among all deliveries in both periods. Groups 2 (nulliparous, single, cephalic, ≥ 37 weeks, induction or CS before labour) and 4 (multiparous excluding previous CS, single, cephalic, ≥ 37 weeks, induction or CS before labour) were less prevalent, however had higher rates of CS. Only in Group 10 (All single, cephalic, ≤ 36 weeks, including previous CS), there was a significant decrease of CS rate from 70.5 to 42.6% between periods.ConclusionRobson's classification did not identify any significant change in the pattern of CS rates with the audit and feedback process, but showed to be useful for comparing trends among similar obstetric populations.
Neglected simultaneous bilateral femoral neck fractures secondary to narcotic drug abuse treated by bilateral one-staged hemiarthroplasty: a case report
Authors: Hootkani Alireza , Moradi Ali , Vahedi Ehsan 
Published: June 2010

AbstractSimultaneous bilateral femoral neck fractures are extremely rare and associated with various conditions. Up to now Most cases had correlations with major trauma, repetitive minor trauma, seizure, parathyroid or renal dysfunction, anti-epileptic medications, seizure, etc. A 28-year-old addict man referred to us with a 10-year history of narcotic drug abuse and history of 8 months bilateral groin pain. He admitted with displaced bilateral femoral neck fracture. Because of long duration of this condition and osteonecrosis revealed on bone scan, one-staged bilateral hip hemiarthroplasty was done. A good function was noted after surgery to 4-month follow up. Up to now, have not be founded in the literature that a case of bilateral femoral neck fracture associated with narcotic drug abuse.Because of negative effects of opium or smoking on bone tissues, a simple bone pain should aware us about the risk of stress or fatigue fracture.
Bleeding from ruptured hepatic metastases as a cause of syncope in an octogenarian: a case report
Authors: Seetho Ian W , Stinchcombe Simon , Rizeq Mazen M 
Published: June 2010

Abstract

Introduction
Acute hemoperitoneum as a result of hemorrhage from liver metastases is an uncommon but serious condition. The use of appropriate imaging is important in the diagnosis and can have a profound impact on subsequent management. This case is important because the presentation was of recurrent syncopal episodes with an unusual underlying cause. This case highlights the need to consider this diagnosis in the differential in patients presenting with collapse in the acute setting.

Case presentation
We present the case of an 85-year-old Caucasian man who was admitted following a collapse episode and was found to be persistently hypotensive despite aggressive resuscitation. An acute intra-peritoneal bleed originating from hepatic metastases from an unknown primary was identified promptly with computed tomography imaging and was subsequently managed conservatively.

Conclusions
This case aims to convey key teaching points: (A) the need to consider intra-abdominal hemorrhage in the differential diagnosis when assessing patients with collapse; and (B) the use of appropriate imaging such as computed tomography can facilitate a prompt diagnosis and appropriate management steps can then be taken accordingly.
Talent or practice: where is the contradiction?
Authors: Pléh Csaba 
Published: June 2010

A dolgozat áttekinti, hogy az utóbbi évtizedek kreativitáskutatása mit mond a tudományos teljesítmény meghatározóiról. Az áttekintés főként D. Simonton munkáira épít. Az egyik visszatérő mozzanat a megszállott produktivitás szerepe a kiválóságban. A korábbi képpel szemben ma a divergens és konvergens folyamatokat egyaránt hangsúlyozzuk a belső meghatározókat illetően. Számos darwini modell a produkció és szelekció ciklusának elválasztását emeli ki. Fontos szerepet kap a társas kontextus és az elfogadás is. Az életutak elemzése a kulturális és történelmi határhelyzetek szerepét állítja előtérbe, valamint a mentorok jelentőségét.
Pore-pressure generation in cyclic T-bar tests on clayey soil
Authors: Oliveira J R M S , Almeida M S S 
Published: June 2010

A model miniature T-bar penetrometer, designed for in-flight applications at the COPPE geotechnical centrifuge in Rio de Janeiro, Brazil, comprises a cylindrical crossbar of 15·2 mm diameter and 112·5 mm long, attached at right angles to the end of a vertical shaft. During penetration, the resistance is measured by a sensitive load cell situated at the vertical shaft immediately above the crossbar. Additionally, a set of two Kulite miniature pore-pressure transducers have been inserted inside the cylindrical crossbar, one at each side of the vertical shaft, facing the bottom part of it. This paper presents a set of cyclic T-bar penetration tests carried out on an artificial clayey soil made of 20% bentonite and 80% kaolin. The generated excess pore pressures are measured at both sides of the bar during the penetration cycles, and compared with values found in the literature. The maximum excess pore pressure, as well as the peak soil resistance, show a significant decrease during soil cyclic penetration. The variations in the excess pore pressure due to the cyclic penetration of the T-bar were also monitored using additional pore-pressure transducers, which were fixed at the bottom of the soil layer. The results were compared with the measurements obtained from the pore-pressure transducers located on the cylindrical crossbar.
Multifront Assault on Antigen Presentation by Japanese Encephalitis Virus Subverts CD8+ T Cell Responses
Authors: Aleyas Abi G. , Han Young Woo , George Junu A. , Kim Bumseok , Kim Koanhoi , Lee Chong-Kil , Eo Seong Kug 
Published: June 2010

Abstract
Japanese encephalitis virus (JEV) is a frequent cause of acute and epidemic viral encephalitis. However, there is little information describing the mechanisms by which JEV subverts immune responses that may predispose the host to secondary infections. In this study, we found that JEV induced the subversion of CD8+ T cell responses in a transient manner that was closely correlated with viral multiplication. Subsequently, analysis using a TCR-transgenic system revealed that CD8+ T cells purified from JEV-infected mice showed impaired responses, and that naive CD8+ T cells adoptively transferred into JEV-infected recipients showed less expanded responses. Furthermore, JEV altered the splenic dendritic cell (DC) subpopulation via preferential depletion of CD8α+CD11c+ DCs without changing the plasmacytoid DCs and induced a significant reduction in the surface expression of MHC class II and CD40, but not MHC class I, CD80, and CD86 molecules. Finally, JEV was shown to inhibit the presentation of MHC class I-restricted Ag in DCs, and this immune suppression was ameliorated via the activation of DCs by TLR agonists. Collectively, our data indicate that JEV precludes the functions of Ag-presenting machinery, such as depletion of CD8α+CD11c+ DCs and downregulation of MHC class I-restricted Ag presentation, thereby leading to immune subversion of CD8+ T cells.
Dyslipidemia Induces Opposing Effects on Intrapulmonary and Extrapulmonary Host Defense through Divergent TLR Response Phenotypes
Authors: Madenspacher Jennifer H. , Draper David W. , Smoak Kathleen A. , Li Haitao , Griffiths Gary L. , Suratt Benjamin T. , Wilson Martha D. , Rudel Lawrence L. , Fessler Michael B. 
Published: June 2010

Abstract
Dyslipidemia influences innate immune responses in the bloodstream, but whether and how pulmonary innate immunity is sensitive to circulating lipoproteins is largely unknown. To define whether dyslipidemia impacts responses to bacteria in the airspace and, if so, whether differently from its effects in other tissues, airspace, bloodstream, and i.p. responses to LPS and Klebsiella pneumoniae were investigated using murine models of dyslipidemia. Dyslipidemia reduced neutrophil (PMN) recruitment to the airspace in response to LPS and K. pneumoniae by impairing both chemokine induction in the airspace and PMN chemotaxis, thereby compromising pulmonary bacterial clearance. Paradoxically, bacteria were cleared more effectively from the bloodstream during dyslipidemia. This enhanced systemic response was due, at least in part, to basal circulating neutrophilia and basal TLR4/MyD88-dependent serum cytokine induction and enhanced serum cytokine responses to systemically administered TLR ligands. Dyslipidemia did not globally impair PMN transvascular trafficking to, and host defense within all loci, because neutrophilia, cytokine induction, and bacterial clearance were enhanced within the infected peritoneum. Peritoneal macrophages from dyslipidemic animals were primed for more robust TLR responses, reflecting increased lipid rafts and increased TLR4 expression, whereas macrophages from the airspace, in which cholesterol was maintained constant during dyslipidemia, had normal responses and rafts. Dyslipidemia thus imparts opposing effects upon intra- and extrapulmonary host defense by inducing tissue-divergent TLR response phenotypes and dysregulating airspace/blood compartmental levels of PMNs and cytokines. We propose that the airspace is a “privileged” site, thereby uniquely sensitive to dyslipidemia.