bluuebunny/crossref_metadata_2025_split huggingface dataset:
Advantages of flow cytometry immunophenotyping for the diagnosis of central nervous system non‐Hodgkin's lymphoma in AIDS patients
Authors: Subirá D , Górgolas M , Castañón S , Serrano C , Román A , Rivas F , Tomás JF 
Published: January 2005

BackgroundNeurological disorders are common in HIV‐infected patients. Central nervous system (CNS) lymphoma should always be considered because it is an important cause of morbidity and mortality.ObjectivesTo investigate the clinical utility of flow cytometry immunophenotyping (FCI) in diagnosing or discarding leptomeningeal involvement in HIV‐infected patients and to compare its sensitivity with that of conventional cytological methods.MethodsFifty‐six cerebrospinal fluid (CSF) samples from 29 HIV‐infected patients were independently evaluated by flow cytometry and cytology. The description of an aberrant immunophenotype was the criterion used to define the malignant nature of any CSF cell population.ResultsFCI and cytology gave concordant results for 48 of the 56 CSF samples studied: 37 were negative for malignancy and 11 had evidence of CNS lymphoma. Discordant results were obtained for eight CSF samples, and the accuracy of the FCI findings could be demonstrated for four CSF samples described as positive for malignancy according to the FCI criteria.ConclusionsA high level of agreement was found between the results obtained using the two methods, but FCI gave at least 25% higher sensitivity than conventional cytomorphological methods for the detection of malignant cells. This advantage suggests that, in case of negative flow cytometry results, disorders other than non‐Hodgkin's lymphoma should be strongly considered.
Chlamydia pneumoniae infection in HIV‐positive patients: prevalence and relationship with lipid profile
Authors: Tositti G , Rassu M , Fabris P , Giordani MT , Cazzavillan S , Reatto P , Zoppelletto M , Bonoldi M , Baldo V , Manfrin V , De Lalla F 
Published: January 2005

ObjectivesThe aims of this study were to evaluate the prevalence and impact of Chlamydia pneumoniae infection in HIV‐positive patients and to establish the relationship between C. pneumoniae infection and lipid profile.MethodsDetection of C. pneumoniae was by polymerase chain reaction (PCR) on Peripheral Blood Mononuclear Cells (PBMCs) collected from 97 HIV‐positive patients. Samples were collected after overnight fast in EDTA‐treated tubes. On the same day, patients were also tested for routine chemistry, HIV viral load, CD3, CD8 and CD4 cell counts and lipid profile [cholesterol, high‐density lipoproteins (HDLs), low‐density lipoproteins (LDLs) and triglycerides].ResultsThe overall prevalence of C. pneumoniae was 39%. The prevalence of C. pneumoniae was inversely related to the CD4 lymphocyte count (P=0.03). In the naive group, C. pneumoniae‐positive patients had both significantly higher HIV load (71 021±15 327 vs. 14 753±14 924 HIV‐1 RNA copies/mL; P=0.03) and lower CD4 cell count (348.0±165.4 vs. 541.7±294.8; P=0.04) than C. pneumoniae‐negative patients. Moreover, treatment‐naive patients with C. pneumoniae infection had significantly higher mean levels of cholesterol (185.3±56.2 vs. 124.8±45.9 mg/dL; P=0.01), triglycerides (117.2±74.7 vs. 68±27.6 mg/dL; P=0.04) and LDL (122.4±60.1 vs. 55.6±58 mg/dL; P=0.05) than C. pneumoniae‐negative patients.ConclusionsThese data indicate that, in HIV‐positive subjects, C. pneumoniae infection is relatively frequent and is associated with both low CD4 cell count and high HIV load. Furthermore, C. pneumoniae appears to be associated with hyperlipidaemia and might therefore represent a further risk factor for cardiovascolar disease in HIV‐positive patients.
Protease inhibitor exposure and increased risk of cardiovascular disease in HIV‐infected patients
Authors: Iloeje UH , Yuan Y , L'Italien G , Mauskopf J , Holmberg SD , Moorman AC , Wood KC , Moore RD 
Published: January 2005

ObjectivesTo study the relationship between exposure to protease inhibitor (PI) therapy and increased risk of cardiovascular events in HIV‐infected patients.MethodsWe estimated the risk of cardiovascular disease (CVD) events with PI exposure in a cohort of HIV‐infected patients using a time‐dependent Cox proportional hazards model adjusting for the major CVD risk factors. Only the first CVD event for each subject was counted.ResultsOf a total of 7542 patients, 77% were exposed to PIs. CVD event rates were 9.8/1000 and 6.5/1000 person–years of follow‐up (PYFU) in the PI‐exposed and nonexposed groups, respectively (P=0.0008). PI exposure ≥60 days was associated with an increased risk of CVD event [adjusted hazards ratio (HRadj) 1.71; 95% confidence interval (CI) 1.08–2.74; P=0.03]. Results from a subgroup of patients aged between 35 and 65 years were similar (HRadj 1.90; 95% CI 1.13–3.20; P=0.02). Other significant risk factors included smoking status, age, hypertension, diabetes mellitus and pre‐existing CVD.ConclusionsPatients exposed to PI therapy had an increased risk of CVD events. Clinicians should evaluate the risk of CVD when making treatment decisions for HIV‐infected patients.
ON PREDICTABILITY OF PARTICLE CLUSTERS IN A STOCHASTIC FLOW
Authors: PITERBARG LEONID I. 
Published: January 2005

In many physical applications it is important to predict particle trajectories in a turbulent flow using a numerical model of the flow. One of the major reasons for a poor prediction is the limited resolution in space. We discuss the problem of predictability limits in the framework of a stochastic flow modeling inertial particles in turbulence. Two stochastic flows called the "model" and "true" are considered. The "model" flow is the "true" flow smoothed in space. The principal measure of discrepancy of the flows is the distance between the centers of mass of two initially identical particle clusters driven by the "true" and "model" flows respectively. The predictability limit is defined as a moment when this distance exceeds the space correlation scale of the true flow. The main result is a simple formula relating the predictability limit with the smoothing scale. This relation is well supported by stochastic simulations and could be a helpful tool in planning experiments in numerical models of turbulent flows. Also the difference between particle scattering in the "true" and "model" flows is studied.
RANDOM SHUFFLING OF SWITCHING PARAMETERS IN A MODEL OF GENE EXPRESSION REGULATORY NETWORK
Authors: VOLCHENKOV D. , LIMA R. 
Published: January 2005

A discrete time model of large gene expression regulatory networks is considered. Transcriptional degrees of regulations and activation thresholds are shuffled randomly that helps to study the highly reproducible dynamical patterns of regulatory processes in a lack of empirical data concerning genetic switches. The multistationarity and multiperiodicity of oscillations exhibited by the system relay upon the feedback circuits. Statistics of their appearance depends upon the relative number of negative regulations between the genes of network, the number of cycles in the maximal graph, and their lengths. The model defined on the scalable graphs demonstrates the high persistence in oscillations and the high error tolerance.
Religious Minorities and Their Rights: A Problem of Approach
Authors: Geoff  
Published: January 2005

AbstractThis article examines the nature of religious minorities and the rights and guarantees accorded to them by public international law generally and, more specifically, international human rights law, particularly since 1945. It is not, though, simply a review of rights pertaining to the group's religious identity, for a difference in religion may reflect the group's sense of national identity. To that end, the rights of religio-nationalist minorities generally are examined: it includes case studies of the ICCPR, the OSCE, the ECHR, the Framework Convention for the Protection of National Minorities, 1995, and the Anglo-Irish Frameworks for the Future. The conclusion, moreover, moves on to consider how international law might best treat religious minorities in order to meet the varied needs of all the parties, that is, the group, the State, the individual members of the minority and majority populations and the international community. It also considers how far law alone can satisfy those varied needs.
One Theme in Two Variations - Self Determination for Minorities And Indigenous Peoples
Authors: Trifunovska  
Published: January 2005

AbstractDuring the 20th century self-determination has become one of the most important principles of international law and one of the most prominent rights on the basis of which (all) peoples can decide freely on their political status and their economic, social and cultural development (Article 1 common to the 1966 ICCPR and ICESCR).Whereas the idea of self-determination is envisaged as an advanced concept aimed at the liberation of peoples under foreign domination in the process of de-colonisation, today's situation and reality call for its reconsideration and adequate clarification with respect to the issues of who is entitled to the right of self-determination and in which forms and to which extent it can be exercised if seen from the aspect of the impact which its exercise might have on the integrity of states. This call is strengthened by the fact that all contemporary states have certain complexity with respect to their national/ethnic/religious/linguistic or racial composition. One of the basic problems in the application of the right of self-determination is created by the fact that there are no definitions in international law on the concepts of various groups. There is no clear answer on what are peoples who are entitled to the right of self-determination, nor is there an accepted definition for other groups which are politically relevant, like indigenous peoples and/or minorities. This may cause serious difficulties since such a lack of clarity provides conditions for persistent claims on the part of groups other than peoples on the right of self-determination, which sometimes threatens territorial integrity of states.
Determination of Formic and Acetic Acid in the Interior Atmosphere of Display Cases and Cabinets in Athens Museums by Reverse Phase High Performance Liquid Chromatography
Authors: Dremetsika Assimina V. , Siskos Panayotis A. , Bakeas Evangelos B. 
Published: January 2005

Formic and acetic acid levels were determined in 15 display cases and 5 cabinets of the National Archaeological Museum and the Numismatic Museum of Athens after both active and passive sampling. Low volume air samplers with solid sorbent silica gel tubes and activated charcoal personal passive samplers were used.The organic acids were analysed by Reverse Phase High Performance Liquid Chromatography with phosphate buffer (pH = 2.5) as the mobile phase and UV detection at 210nm. Formic acid concentrations in display cases and cabinets ranged from 0.03 to 0.18mg·m−3, and acetic acid concentrations ranged from 0.06 to 2.42mg·m−3.
Posttranslational modifications of p27kip1 determine its binding specificity to different cyclins and cyclin-dependent kinases in vivo
Authors: Zhang Wenqing , Bergamaschi Daniele , Jin Boquan , Lu Xin 
Published: January 2005

AbstractUsing 2-dimensional gel electrophoresis (2D-gel) analysis, we show here that cell-cycle entry is associated with a significant increase in p27kip1 phosphorylation in human primary B cells. A similar pattern of increase in p27kip1 phosphorylation was also seen in 2 fast-growing tumor cell lines, Burkitt lymphoma cell line BL40 and breast carcinoma cell line Cal51, where inactive p27kip1 is expressed at high levels. Detailed analysis revealed for the first time that different cyclins and cyclin-dependent kinases (cdk's) interact with distinct posttranslationally modified isoforms of p27kip1 in vivo. Cyclin E but not cyclin A selectively interacts with phosphorylated p27kip1 isoforms, while cyclin D1 and D2 favor unphosphorylated p27kip1 isoforms in vivo. Interestingly, cyclin D3 and cdk4 selectively interact with phosphorylated p27kip1 in BL40 cells. Among all D-type cyclin/cdk4 and cdk6 complexes, cyclin D3/cdk4 is most active in sequestering the inhibitory activity of p27kip1 in vitro in a cyclinE/cdk2 kinase assay. This novel feature of the binding specificity of p27kip1 to cyclins and cdk's in vivo is interpreted in the context of overexpression of cyclin D3 in the presence of high levels of p27kip1 in human B-cell lymphomas with adverse clinical outcome.
A pathobiologic pathway linking thrombopoietin, GATA-1, and TGF-β1 in the development of myelofibrosis
Authors: Vannucchi Alessandro M. , Bianchi Lucia , Paoletti Francesco , Pancrazzi Alessandro , Torre Eugenio , Nishikawa Mitsuo , Zingariello Maria , Di Baldassarre Angela , Rana Rosa Alba , Lorenzini Rodolfo , Alfani Elena , Migliaccio Giovanni , Migliaccio Anna Rita 
Published: January 2005

AbstractIdiopathic myelofibrosis (IM) is a disease characterized by marrow fibrosis, abnormal stem/progenitor cell trafficking, and extramedullary hematopoiesis frequently associated with alterations in megakaryocytes (Mks). Mice harboring genetic alterations in either the extrinsic (ectopic thrombopoietin expression, TPOhigh mice) or intrinsic (hypomorphic GATA-1 mutation, GATA-1low mice) control of Mk differentiation develop myelofibrosis, a syndrome similar to IM. The relationship, if any, between the pathobiologic mechanism leading to the development of myelofibrosis in the 2 animal models is not understood. Here we show that plasma from GATA-1low mice contained normal levels of TPO. On the other hand, Mks from TPO-treated wild-type animals (TPOhigh mice), as those from GATA-1low animals, had similar morphologic abnormalities and contained low GATA-1. In both animal models, development of myelofibrosis was associated with high transforming growth factor β1 (TGF-β1) content in extracellular fluids of marrow and spleen. Surprisingly, TPO treatment of GATA-1low mice restored the GATA-1 content in Mks and halted both defective thrombocytopoiesis and fibrosis. These data indicate that the TPOhigh and GATA-1low alterations are linked in an upstream-downstream relationship along a pathobiologic pathway leading to development of myelofibrosis in mice and, possibly, of IM in humans.
Membrane type 1–matrix metalloproteinase is involved in migration of human monocytes and is regulated through their interaction with fibronectin or endothelium
Authors: Matías-Román Salomón , Gálvez Beatriz G. , Genís Laura , Yáñez-Mó María , de la Rosa Gonzalo , Sánchez-Mateos Paloma , Sánchez-Madrid Francisco , Arroyo Alicia G. 
Published: January 2005

AbstractMembrane type 1–matrix metalloproteinase (MT1-MMP) is involved in endothelial and tumor-cell migration, but its putative role in leukocyte migration has not been characterized yet. Here, we demonstrate that anti–MT1-MMP monoclonal antibody (mAb) impaired monocyte chemotactic protein-1 (MCP-1)–stimulated monocyte migration on fibronectin (FN), vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1). In addition, monocyte transmigration through tumor necrosis factor-α (TNF-α)–activated endothelium is also inhibited by anti–MT1-MMP mAb. Therefore, regulation of MT1-MMP in human peripheral blood monocytes was investigated. First, MT1-MMP clustering was observed at motility-associated membrane protrusions of MCP-1–stimulated monocytes migrating on FN, VCAM-1, or ICAM-1 and at the leading edge, together with profilin, of monocytes transmigrating through activated endothelial cells. In addition, up-regulation of MT1-MMP expression was induced in human monocytes upon attachment to FN in a manner dependent on α4β1 and α5β1 integrins. Binding of monocytes to TNF-α–activated human endothelial cells as well as to VCAM-1 or ICAM-1 also resulted in an increase of MT1-MMP expression. These findings correlated with an enhancement of MT1-MMP fibrinolytic activity in monocytes bound to FN, VCAM-1, or ICAM-1. Our data show that MT1-MMP is required during human monocyte migration and endothelial transmigration and that MT1-MMP localization, expression, and activity are regulated in monocytes upon contact with FN or endothelial ligands, pointing to a key role of MT1-MMP in monocyte recruitment during inflammation.
Activation of Src kinase Lyn by the Kaposi sarcoma–associated herpesvirus K1 protein: implications for lymphomagenesis
Authors: Prakash Om , Swamy O. Rama , Peng Xiochang , Tang Zhen-Ya , Li Li , Larson Janet E. , Cohen J. Craig , Gill Javed , Farr Gist , Wang Suizhao , Samaniego Felipe 
Published: January 2005

AbstractThe K1 gene of Kaposi sarcoma–associated herpesvirus (KSHV) encodes a transmembrane glycoprotein bearing a functional immunoreceptor tyrosine-based activation motif (ITAM). Previously, we reported that the K1 protein induced plasmablastic lymphomas in K1 transgenic mice, and that these lymphomas showed enhanced Lyn kinase activity. Here, we report that systemic administration of the nuclear factor kappa B (NF-κB) inhibitor Bay 11-7085 or an anti–vascular endothelial growth factor (VEGF) antibody significantly reduced K1 lymphoma growth in nude mice. Furthermore, in KVL-1 cells, a cell line derived from a K1 lymphoma, inhibition of Lyn kinase activity by the Src kinase inhibitor PP2 decreased VEGF induction, NF-κB activity, and the cell proliferation index by 50% to 75%. In contrast, human B-cell lymphoma BJAB cells expressing K1, but not the ITAM sequence–deleted mutant K1, showed a marked increase in Lyn kinase activity with concomitant VEGF induction and NF-κB activation, indicating that ITAM sequences were required for the Lyn kinase–mediated activation of these factors. Our results suggested that K1-mediated constitutive Lyn kinase activation in K1 lymphoma cells is crucial for the production of VEGF and NF-κB activation, both strongly implicated in the development of KSHV-induced lymphoproliferative disorders.
Pharmacologic inhibitors of PI3K/Akt potentiate the apoptotic action of the antileukemic drug arsenic trioxide via glutathione depletion and increased peroxide accumulation in myeloid leukemia cells
Authors: Ramos Adrián M. , Fernández Carlos , Amrán Donna , Sancho Patricia , de Blas Elena , Aller Patricio 
Published: January 2005

AbstractTreatment for 14 to 24 hours with low concentrations of arsenic trioxide (As2O3, 1-4 μM) caused apoptosis in U-937 promonocytes and other human myeloid leukemia cell lines (HL-60, NB4). This effect was potentiated by cotreatment with the phosphatidylinositol 3-kinase (PI3K) inhibitors LY294002 and wortmannin, and the Akt inhibitor Akti5. However, the inhibitors did not increase the toxicity of the mitochondria-targeting drug lonidamine, and the DNA-specific drugs camptothecin and cisplatin, when used under similar experimental conditions as As2O3. The potentiation of As2O3-provoked apoptosis involved the increased disruption of mitochondrial transmembrane potential, increased caspase-3 activation and cytochrome c release from mitochondria, increased Bax and Bid activation, and attenuation of 27-kDa heat shock protein (HSP27) expression; the potentiation was prevented by Bcl-2 overexpression. The PI3K/Akt inhibitors decreased the intracellular glutathione content, and caused intracellular oxidation, as measured by peroxide accumulation. Cotreatment with subcytotoxic concentrations of hydrogen peroxide increased apoptosis induction by As2O3. On the other hand, the treatments did not significantly affect glutathione S-transferase π expression and activity. These results, which indicate that glutathione is a target of PI3K/Akt in myeloid leukemia cells, may partially explain the selective increase of As2O3 toxicity by PI3K/Akt inhibitors, and may provide a rationale to improve the efficacy of these inhibitors as therapeutic agents.
Hereditary hemochromatosis is reflected in the iron isotope composition of blood
Authors: Krayenbuehl Pierre-Alexandre , Walczyk Thomas , Schoenberg Ronny , von Blanckenburg Friedhelm , Schulthess Georg 
Published: January 2005

Abstract
It has recently been shown that the iron isotopic composition of blood differs between individuals and sexes, which is supposed to reflect individual differences in iron metabolism. We hypothesized that patients suffering from hereditary hemochromatosis would demonstrate alterations in the iron isotopic composition of blood due to persistent up-regulation of intestinal iron absorption. Blood from 30 patients with homozygous C282Y hemochromatosis was analyzed for iron isotopic composition by a newly developed technique using multicollector inductively coupled plasma mass spectrometry (MC-ICP-MS). Blood of patients with hemochromatosis is characterized by a higher 56Fe/54Fe isotope ratio than blood of healthy individuals, which are either members of an age-matched control group (n = 10; P &lt; .001) or young adults (n = 36; P &lt; .001). In patients with hereditary hemochromatosis, the 56Fe/54Fe isotope ratio of blood significantly correlates with total-body iron accumulation, severity of clinical disease, and the need for regular phlebotomies to prevent iron reaccumulation. We conclude that blood of patients with hereditary hemochromatosis contains more of the heavier iron isotopes than blood of healthy individuals. The primary determinant of the iron isotopic composition of blood appears to be isotope-sensitive iron absorption in the intestine and the efficiency of this process.
P2Y1 and P2Y12 receptors for ADP desensitize by distinct kinase-dependent mechanisms
Authors: Hardy Adam R. , Conley Pamela B. , Luo Jiansong , Benovic Jeffrey L. , Poole Alastair W. , Mundell Stuart J. 
Published: January 2005

AbstractAdenosine 5′-diphosphate (ADP) plays a central role in regulating platelet function by the activation of the G protein–coupled receptors P2Y1 and P2Y12. Although it is well established that aggregation responses of platelets to ADP desensitize, the underlying mechanisms involved remain unclear. In this study we demonstrate that P2Y1- and P2Y12-mediated platelet responses desensitize rapidly. Furthermore, we have established that these receptors desensitize by different kinase-dependent mechanisms. G protein–coupled receptor kinase (GRK) 2 and GRK6 are both endogenously expressed in platelets. Transient overexpression of dominant-negative mutants of these kinases or reductions in endogenous GRK expression by the use of specific siRNAs in 1321N1 cells showed that P2Y12, but not P2Y1, desensitization is mediated by GRKs. In contrast, desensitization of P2Y1, but not P2Y12, is largely dependent on protein kinase C activity. This study is the first to show that both P2Y1 and P2Y12 desensitize in human platelets, and it reveals ways in which their sensitivity to ADP may be differentially and independently altered.