bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activation of αIIbβ3 is a sufficient but also an imperative prerequisite for activation of α2β1 on platelets
Authors: Van de Walle Gerlinde R. , Schoolmeester Anne , Iserbyt Brecht F. , Cosemans Judith M. E. M. , Heemskerk Johan W. M. , Hoylaerts Marc F. , Nurden Alan , Vanhoorelbeke Karen , Deckmyn Hans 
Published: September 2006

AbstractPlatelet integrins α2β1 and αIIbβ3 play critical roles in platelet adhesion and thrombus formation after vascular injury. On resting platelets, both integrins are in a low-affinity state. However, agonist stimulation results in conformational changes that enable ligand binding that can be detected with conformation dependent monoclonal antibodies (mAbs). By using such conformation-dependent mAbs, we could demonstrate that activation of integrin αIIbβ3 is not only sufficient, but also a prerequisite for α2β1 activation. Compared with platelets in plasma, stimulation of washed platelets resulted in only a minor activation of α2β1, as detected with the activation-sensitive mAb IAC-1. Addition of fibrinogen to stimulated washed platelets greatly potentiated activation of this integrin. Also, treatment of αIIbβ3 with the ligand-mimetic peptide RGDS, resulting in outside-in signaling, led to a powerful α2β1 activation, even in the absence of overall platelet activation, involving tyrosine kinase activity but no protein kinase C activation. The absolute necessity of αIIbβ3 for proper α2β1 activation on platelets was demonstrated by using the αIIbβ3 antagonist aggrastat, which was able to completely abolish α2β1 activation, both under static and flow conditions. In addition, analogous experiments with Glanzmann platelets lacking αIIbβ3 confirmed the indispensability of αIIbβ3 for α2β1 activation.
Therapy-related myelodysplasia and acute myeloid leukemia after Ewing sarcoma and primitive neuroectodermal tumor of bone: a report from the Children's Oncology Group
Authors: Bhatia Smita , Krailo Mark D. , Chen Zhengjia , Burden Laura , Askin Frederic B. , Dickman Paul S. , Grier Holcombe E. , Link Michael P. , Meyers Paul A. , Perlman Elizabeth J. , Rausen Aaron R. , Robison Leslie L. , Vietti Teresa J. , Miser James S. 
Published: September 2006

Abstract
This study describes the magnitude of risk of therapy-related myelodysplasia and acute myeloid leukemia (t-MDS/AML) in 578 individuals diagnosed with Ewing sarcoma and enrolled on Children's Oncology Group therapeutic protocol, INT-0091. Between 1988 and 1992, patients with or without metastatic disease were randomized to receive doxorubicin, vincristine, cyclophosphamide, and dactinomycin (regimen A) or these 4 drugs alternating with etoposide and ifosfamide (regimen B). Between 1992 and 1994, patients with metastatic disease were nonrandomly assigned to receive high-intensity therapy (regimen C: regimen B therapy with higher doses of doxorubicin, cyclophosphamide, and ifosfamide). Median age at diagnosis of Ewing sarcoma was 12 years, and median length of follow-up, 8 years. Eleven patients developed t-MDS/AML, resulting in a cumulative incidence of 2% at 5 years. While patients treated on regimens A and B were at a low risk for development of t-MDS/AML (cumulative incidence: 0.4% and 0.9% at 5 years, respectively), patients treated on regimen C were at a 16-fold increased risk of developing t-MDS/AML (cumulative incidence: 11% at 5 years), when compared with those treated on regimen A. Increasing exposure to ifosfamide from 90 to 140 g/m2, cyclophosphamide from 9.6 to 17.6 g/m2, and doxorubicin from 375 to 450 mg/m2 increased the risk of t-MDS/AML significantly.
Human CD4+CD25+ regulatory T cells selectively express tyrosine hydroxylase and contain endogenous catecholamines subserving an autocrine/paracrine inhibitory functional loop
Authors: Cosentino Marco , Fietta Anna Maria , Ferrari Marco , Rasini Emanuela , Bombelli Raffaella , Carcano Elena , Saporiti Federica , Meloni Federica , Marino Franca , Lecchini Sergio 
Published: September 2006

AbstractCD4+CD25+ regulatory T lymphocytes (Tregs) are specialized T cells playing a key role in the control of immune homeostasis. Here, we show that human Tregs constitutively express tyrosine hydroxylase (TH, EC 1.14.16.2), the rate-limiting enzyme in the synthesis of catecholamines, and contain substantial amounts of dopamine, norepinephrine, and epinephrine, which are released upon treatment with reserpine. Catecholamine release results in reduced production of interleukin-10 and transforming growth factor-β by Tregs, and in down-regulation of Treg-dependent inhibition of effector T-lymphocyte (Teff) proliferation, which occurs without affecting the production of tumor necrosis factor-α or interferon-γ. Tregs and Teffs express on the cell membrane both D1-like and D2-like dopaminergic receptors to a similar extent (12%-29% of the cells). Catecholamine-dependent down-regulation of Tregs is, however, selectively reversed by pharmacological blockade of dopaminergic D1-like receptors, which in Tregs only (and not in Teffs) are also expressed at the level of mRNA and are functionally coupled to intracellular production of cAMP. These findings indicate that in human Tregs endogenous catecholamines subserve an autocrine/paracrine loop involving dopaminergic pathways and resulting in down-regulation of Treg function.
Incidence of CSF3R mutations in severe congenital neutropenia and relevance for leukemogenesis: results of a long-term survey
Authors: Germeshausen Manuela , Ballmaier Matthias , Welte Karl 
Published: September 2006

AbstractPoint mutations in the gene for the granulocyte colony-stimulating factor (G-CSF) receptor CSF3R have been implicated in the progression of severe congenital neutropenia (CN) to leukemia. In this study we present data on a total of 218 patients with chronic neutropenia, including 148 patients with CN (23/148 with secondary malignancies). We detected CSF3R nonsense mutations at 17 different nucleotide positions (thereof 10 new mutations) which lead to a loss of 1 to all 4 tyrosine residues in the intracellular domain of the receptor. Of 23 patients with CN with signs of malignant transformation, 18 (78%) were shown to harbor a CSF3R mutation, indicating that these mutations, although not a necessary condition, are highly predictive for malignant transformation even if detected in a low percentage of transcripts. In serial analyses of 50 patients with CSF3R mutations we were able to follow the clonal dynamics of mutated cells. We could demonstrate that even a highly clonal hematopoiesis did not inevitably show a rapid progression to leukemia. Our results strongly suggest that acquisition of a CSF3R mutation is an early event in leukemogenesis that has to be accompanied by cooperating molecular events, which remain to be defined.
Current concepts on the pathogenesis of the antiphospholipid syndrome
Authors: Giannakopoulos Bill , Passam Freda , Rahgozar Soheila , Krilis Steven A. 
Published: September 2006

AbstractThe antiphospholipid syndrome (APS) is an important cause of acquired thrombophilia. It is characterized by the core clinical manifestations of thrombosis, either venous or arterial, and in women it can also be associated with recurrent fetal loss. The detection of persistently elevated levels of antiphospholipid antibodies (aPL Abs) is a requisite laboratory feature for the diagnosis to be made. The dominant antigenic targets in APS are beta 2-glycoprotein I (β2-GPI) and prothrombin. There is an accumulating body of experimental evidence that suggests that specific subgroups of aPL Abs may directly contribute to disease pathogenesis. This review critically examines the experimental evidence underlying the various propositions made to explain how these antibodies may predispose to disease in humans. Furthermore, it also examines the evidence relating to the immunologic mechanisms that may contribute to the breakage of peripheral tolerance in this disorder. Delineating the strengths and limitations of the experimental evidence accumulated thus far will hopefully stimulate further experimentation toward achieving the ultimate goal of precisely defining the dominant pathogenic mechanisms operational in APS. This may pave the way for the development of improved therapies.
Tumor necrosis factor α triggers proliferation of adult neural stem cells via IKK/NF-κB signaling
Authors: Widera Darius , Mikenberg Ilja , Elvers Margitta , Kaltschmidt Christian , Kaltschmidt Barbara 
Published: September 2006

AbstractBackgroundBrain inflammation has been recognized as a complex phenomenon with numerous related aspects. In addition to the very well-described neurodegenerative effect of inflammation, several studies suggest that inflammatory signals exert a potentially positive influence on neural stem cell proliferation, migration and differentiation. Tumor necrosis factor alpha (TNF-α) is one of the best-characterized mediators of inflammation. To date, conclusions about the action of TNF on neural stem or progenitor cells (NSCs, NPCs) have been conflicting. TNF seems to activate NSC proliferation and to inhibit their differentiation into NPCs. The purpose of the present study was to analyze the molecular signal transduction mechanisms induced by TNF and resulting in NSC proliferation.ResultsHere we describe for the first time the TNF-mediated signal transduction cascade in neural stem cells (NSCs) that results in increased proliferation. Moreover, we demonstrate IKK-α/β-dependent proliferation and markedly up-regulated cyclin D1 expression after TNF treatment. The significant increase in proliferation in TNF-treated cells was indicated by increased neurosphere volume, increased bromodeoxyuridin (BrdU) incorporation and a higher total cell number. Furthermore, TNF strongly activated nuclear factor-kappa B (NF-κB) as measured by reporter gene assays and by an activity-specific antibody. Proliferation of control and TNF-treated NSCs was strongly inhibited by expression of the NF-κB super-repressor IκB-AA1. Pharmacological blockade of IκB ubiquitin ligase activity led to comparable decreases in NF-κB activity and proliferation. In addition, IKK-β gene product knock-down via siRNA led to diminished NF-κB activity, attenuated cyclin D1 expression and finally decreased proliferation. In contrast, TGFβ-activated kinase 1 (TAK-1) is partially dispensable for TNF-mediated and endogenous proliferation. Understanding stem cell proliferation is crucial for future regenerative and anti-tumor medicine.ConclusionTNF-mediated activation of IKK-β resulted in activation of NF-κB and was followed by up-regulation of the bona-fide target gene cyclin D1. Activation of the canonical NF-κB pathway resulted in strongly increased proliferation of NSCs.
Managerial attitude to the implementation of quality management systems in Lithuanian support treatment and nursing hospitals
Authors: Buciuniene Ilona , Malciankina Sonata , Lydeka Zigmas , Kazlauskaite Ruta 
Published: September 2006

Abstract

Background
The regulations of the Quality Management System (QMS) implementation in health care organizations were approved by the Lithuanian Ministry of Health in 1998. Following the above regulations, general managers of health care organizations had to initiate the QMS implementation in hospitals. As no research on the QMS implementation has been carried out in Lithuanian support treatment and nursing hospitals since, the objective of this study is to assess its current stage from a managerial perspective.

Methods
A questionnaire survey of general managers of Lithuanian support treatment and nursing hospitals was carried out in the period of January through March 2005. Majority of the items included in the questionnaire were measured on a seven-point Likert scale. During the survey, a total of 72 questionnaires was distributed, out of which 58 filled-in ones were returned (response rate 80.6 per cent; standard sampling error 0.029 at 95 per cent level of confidence).

Results
Quality Management Systems were found operating in 39.7 per cent of support treatment and nursing hospitals and currently under implementation in 46.6 per cent of hospitals (13.7% still do not have it). The mean of the respondents' perceived QMS significance is 5.8 (on a seven-point scale). The most critical issues related to the QMS implementation include procedure development (5.5), lack of financial resources (5.4) and information (5.1), and development of work guidelines (4.6), while improved responsibility and power sharing (5.2), better service quality (5.1) and higher patient satisfaction (5.1) were perceived by the respondents as the key QMS benefits. The level of satisfaction with the QMS among the management of the surveyed hospitals is mediocre (3.6). However it was found to be higher among respondents who were more competent in quality management, were familiar with ISO 9000 standards, and had higher numbers of employees trained in quality management.

Conclusion
QMSs are perceived to be successfully running in one third of the Lithuanian support treatment and nursing hospitals. Its current implementation stage is dependent on the hospital size – the bigger the hospital the more success it meets in the QMS implementation. As to critical Quality Management (QM) issues, hospitals tend to encounter such major problems as lack of financial resources, information and training, as well as difficulties in procedure development. On the other hand, the key factors that assist to the success of the QMS implementation comprise managerial awareness of the QMS significance and the existence of employee training systems and audit groups in hospitals.
A comprehensive analysis of the androgen receptor gene and risk of breast cancer: results from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3)
Authors: Cox David G , Blanché Hélène , Pearce Celeste L , Calle Eugenia E , Colditz Graham A , Pike Malcolm C , Albanes Demetrius , Allen Naomi E , Amiano Pilar , Berglund Goran , Boeing Heiner , Buring Julie , Burtt Noel , Canzian Federico , Chanock Stephen , Clavel-Chapelon Françoise , Feigelson Heather Spencer , Freedman Matthew , Haiman Christopher A , Hankinson Susan E , Henderson Brian E , Hoover Robert , Hunter David J , Kaaks Rudolf , Kolonel Laurence , Kraft Peter , LeMarchand Loic , Lund Eiliv , Palli Domenico , Peeters Petra HM , Riboli Elio , Stram Daniel O , Thun Michael , Tjonneland Anne , Trichopoulos Dimitrios , Yeager Meredith ,   the Breast and Prostate Cancer Cohort Consortium
Published: September 2006

Abstract
Introduction
Androgens have been hypothesised to influence risk of breast cancer through several possible mechanisms, including their conversion to estradiol or their binding to the oestrogen receptor and/or androgen receptor (AR) in the breast. Here, we report on the results of a large and comprehensive study of the association between genetic variation in the AR gene and risk of breast cancer in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3).

Methods
The underlying genetic variation was determined by first sequencing the coding regions of the AR gene in a panel of 95 advanced breast cancer cases. Second, a dense set of markers from the public database was genotyped in a panel of 349 healthy women. The linkage disequilibrium relationships (blocks) across the gene were then identified, and haplotype-tagging single nucleotide polymorphisms (htSNPs) were selected to capture the common genetic variation across the locus. The htSNPs were then genotyped in the nested breast cancer cases and controls from the Cancer Prevention Study II, European Prospective Investigation into Cancer and Nutrition, Multiethnic Cohort, Nurses' Health Study, and Women's Health Study cohorts (5,603 breast cancer cases and 7,480 controls).

Results
We found no association between any genetic variation (SNP, haplotype, or the exon 1 CAG repeat) in the AR gene and risk of breast cancer, nor were any statistical interactions with known breast cancer risk factors observed.

Conclusion
Among postmenopausal Caucasian women, common variants of the AR gene are not associated with risk of breast cancer.
High Molecular Weight, Rather than Total, Adiponectin Levels Better Reflect Metabolic Abnormalities Associated with Childhood Obesity
Authors: Araki Shunsuke , Dobashi Kazushige , Kubo Kazuyasu , Asayama Kohtaro , Shirahata Akira 
Published: September 2006

Abstract
Context: Japanese are prone to obesity-induced metabolic derangement, which is linked to serum adipocytokine profile even in children.
Objective: The objective of the study was to determine whether high molecular-weight adiponectin (H-Adn) more specifically relates to metabolic derangement in obese children than total adiponectin (T-Adn).
Design and Setting: A case (n = 59) control (n = 28) study was performed at the pediatric clinic of a university hospital.
Patients: Japanese obese children (38 boys and 21 girls) were consecutively enrolled. The ages ranged from 5 to 15 (10.3 ± 0.3; mean ± sem) yr. Nonobese children (15 boys and 13 girls) were assigned as age-matched controls.
Main Outcome Measures: Serum adiponectin multimeric complexes were assayed by an ELISA kit. The relationship of adiponectin to metabolic abnormalities was evaluated.
Results: T-Adn (5.1 ± 0.2 vs. 8.8 ± 0.4 μg/ml), H-Adn (1.3 ± 0.1 vs. 4.8 ± 0.4 μg/ml), and medium molecular weight-Adn were significantly lower in obese than in control children. After adjustment for age and sex, both T- and H-Adn were inversely correlated with insulin and homeostasis model of assessment-insulin resistance, whereas H-Adn (but not T-Adn) inversely correlated with visceral fat area, as determined by computed tomography. Seven obese children were estimated to have metabolic syndrome and showed selective decrease in H-Adn and H/T-Adn.
Conclusion: H-Adn reflects metabolic abnormalities due to obesity better than T-Adn in children. H-Adn is associated with the development of metabolic syndrome, even in childhood.
Crosslinked enzyme aggregates in hierarchically‐ordered mesoporous silica: A simple and effective method for enzyme stabilization
Authors: Kim Moon Il , Kim Jungbae , Lee Jinwoo , Jia Hongfei , Na Hyon Bin , Youn Jong Kyu , Kwak Ja Hun , Dohnalkova Alice , Grate Jay W. , Wang Ping , Hyeon Taeghwan , Park Hyun Gyu , Chang Ho Nam 
Published: September 2006

Abstractα‐chymotrypsin (CT) and lipase (LP) were immobilized in hierarchically‐ordered mesocellular mesoporous silica (HMMS) in a simple but effective way for the enzyme stabilization, which was achieved by the enzyme adsorption followed by glutaraldehyde (GA) crosslinking. This resulted in the formation of nanometer scale crosslinked enzyme aggregates (CLEAs) entrapped in the mesocellular pores of HMMS (37 nm), which did not leach out of HMMS through narrow mesoporous channels (13 nm). CLEA of α‐chymotrypsin (CLEA‐CT) in HMMS showed a high enzyme loading capacity and significantly increased enzyme stability. No activity decrease of CLEA‐CT was observed for 2 weeks under even rigorously shaking condition, while adsorbed CT in HMMS and free CT showed a rapid inactivation due to the enzyme leaching and presumably autolysis, respectively. With the CLEA‐CT in HMMS, however, there was no tryptic digestion observed suggesting that the CLEA‐CT is not susceptible to autolysis. Moreover, CLEA of lipase (CLEA‐LP) in HMMS retained 30% specific activity of free lipase with greatly enhanced stability. This work demonstrates that HMMS can be efficiently employed as host materials for enzyme immobilization leading to highly enhanced stability of the immobilized enzymes with high enzyme loading and activity. Biotechnol. Bioeng. 2007;96: 210–218. © 2006 Wiley Periodicals, Inc.
Screening antimicrobial activity of various extracts of Artemisia dracunculus L.
Authors: Benli Mehlika , Kaya Ilhan , Yigit Nazife 
Published: September 2006

AbstractThe antimicrobial activities of chloroform, acetone and two different concentrations of methanol extracts of Artemisia dracunculus L. were studied. These extracts were tested against nine bacteria and four yeasts strains by the disc diffusion method. The results indicated that the methanol extract of A. dracunculus is more effective against tested microorganisms than chloroform or acetone extracts. The chloroform and acetone extracts were inhibitory only towards Pseudomonas aeruginosa (ATCC 27853). While the methanol extract that was diluted with 10 ml distilled water showed inhibition zones against Shigella (RSHI), Listeria monocytogenes ATCC 7644, P. aeruginosa (ATCC 27853), the methanol extract that was diluted with 5 ml distilled water showed inhibition zones against two different strains of Escherichia coli (RSHI, ATCC 25922), Shigella (RSHI), L. monocytogenes (ATCC 7644), and P. aeruginosa ATCC 27853. The cells of microorganisms treated with plant extracts and normal microorganism cells were observed by scanning electron microscope. It was apparent that cells are damaged after treatment with A. dracunculus. Copyright © 2006 John Wiley & Sons, Ltd.
Supramolecular Assemblies of Sulfonatocalixarenes with Phenanthroline: Factors Governing Capsule Formation versus Bilayer Arrangements
Authors: Liu Yu , Guo Dong‐Sheng , Zhang Heng‐Yi , Ding Fei , Chen Kun , Song Hai‐Bin 
Published: September 2006

AbstractFour crystalline complexes were prepared by the inclusion complexation of the 1,10‐phenanthrolinium ion (Phen) with p‐sulfonatothiacalix[4]arene (TCAS) (2 from a solution at pH 1–2 and 4 from 1 M HCl) and with p‐sulfonatocalix[5]arene (C5AS) (3 from a solution at pH 1–2 and 5 from 1 M HCl) upon varying the acidity of the solution. By combining the results obtained for complexes 2–5 with those for our previously reported complex (1), p‐sulfonatocalix[4]arene (C4AS) complexed to Phen, it was revealed that p‐sulfonatocalixarenes (CASs) form “bis‐molecular” capsules (1, 2, and 3) around Phen at pH 1–2, whereas complexes 4 and 5 display distinct host–guest inclusion behavior at higher acid concentrations. The degree of compactness of the capsules increases with the enlargement of the calixarene cavity, which is affected significantly by both the penetration depth of Phen and the structure of the Phen dimer. Furthermore, the complexation behavior of TCAS/C5AS with Phen in 1 M DCl was investigated by using NMR spectroscopy, and was discussed in comparison with the previously reported results obtained from solutions at pH 2.0.
Synthesis and Structure of Some MII/MIII Mixed Fluorides with Pyrochlore and Weberite Related Structures.
Authors: Subramanian M. A. , Marshall W. J. , Hoffmann R.‐D. , Sleight A. W. 
Published: September 2006

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Rubidium Dimolybdate, Rb2Mo2O7, and Caesium Dimolydate, Cs2Mo2O7.
Authors: Solodovnikova Zoya A. , Solodovnikov Sergey F. 
Published: September 2006

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Commensurate Monoclinic Form of Ca2Zn0.97Co0.03Ge2O7.
Authors: Redhammer Guenther J. , Roth Georg 
Published: September 2006

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
The Isothermal Section of the Er—Fe—Sb Ternary System at 773 K.
Authors: Cai Gemei , Wei Xiangzhong , Zeng Lingmin 
Published: September 2006

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Inverse Perovskite (Ln3N)Sn with Ln: La, Ce, Pr, Nd, Sm: Preparation, Crystal Structures and Physical Properties.
Authors: Kirchner Martin , Schnelle Walter , Niewa Rainer 
Published: September 2006

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.