bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patients with Coronary Artery Disease Have an Increased Incidence of Aspirin Resistance: Association of PFA-100 Closure Time with Clinical Findings.
Authors: Frelinger Andrew L. , Linden Matthew D. , Furman Mark I. , Fox Marsha L. , Barnard Marc R. , Li Youfu , Barringhaus Kurt , Przyklenk Karin , Michelson Alan D. 
Published: October 2019

Abstract
Background: The occurrence of thrombotic events despite aspirin (ASA) therapy in patients with vascular disease has been termed ASA resistance. However, limited data are available correlating laboratory evidence of platelet function with clinical ASA resistance. The PFA-100 collagen/epinephrine (COL/EPI) cartridge can detect the ASA-induced inhibition of platelet cyclooxygenase 1 in a high shear flow environment that mimics in vivo arterial conditions.
Aim: To investigate whether there is an association of PFA-100 test results with clinical ASA resistance.
Methods: Peripheral blood was collected prior to angiography from 560 sequential ASA-treated patients (81 or 325 mg > 3 d). Patients receiving thienopyridines were not excluded but those receiving GPIIb-IIIa antagonists were. Patients with normal angiographic arteries ("No CAD", low probability of ASA resistance) were compared to those with angiographic CAD or a single prior CAD event and to those with multiple CAD events ("CAD" and "Repeat CAD" respectively, higher probability of ASA resistance). Citrate 3.8% anticoagulated blood was tested in the PFA-100 in duplicate using the COL/EPI test cartridge. Patients in the No CAD group were younger, more often female, and less often diabetic, hypertensive, and lipidemic than CAD or Repeat CAD patients.
Results: A short (< 142 s) closure time (CT) in at least one of the duplicate PFA-100 COL/EPI cartridges occurred more frequently in CAD and Repeat CAD patients compared to No CAD patients (p < 0.05, Table).
Conclusions: Failure of ASA to inhibit platelet function, as measured by the PFA-100, is associated with CAD, even in patients without prior history of CAD. The PFA-100, a shear-dependent system, may therefore be a useful test to assess the presence of ASA resistance. This test, unlike some tests for aspirin resistance, does not include ADP and therefore can be used in patients receiving thienopyridines (a frequent co-medication with aspirin).
No CAD CAD Repeat CAD *p<0.05 vs. No CAD PFA-100 CT < 142 s (no. of patients) 4 45 26 PFA-100 CD ≥ 142 s (no. of patients) 79 251 155 Total (no. of patients) 83 296 181 % PFA-100 CT < 142 s 5% 15%* 14%*
The Expression of LI-Cadherin in Bone Marrow Is Correlated with Clinical Outcome in Children with Acute Lymphoblastic Leukemia at First Relapse.
Authors: Wu Shuling , Hernández Anay Marquetti , Dietel Corinna , von Stackelberg Arend , Henze Guenter , Seeger Karl , Gessner Reinhard 
Published: October 2019

Abstract
Liver and Intestine (LI)-cadherin, also termed cadherin-17, is a calcium ion dependent cell-cell adhesion molecule that is highly expressed in the intestinal epithelia but not in the upper gastric tract. Although LI-cadherin is not found in the healthy gastric mucosa, it is ectopically expressed in gastric metaplasia and adenocarcinomas. Recently it was revealed that LI-cadherin expression correlates with gastric cancer progression and lymph node metastasis. In mice LI-cadherin was found to be expressed by B cell progenitor cells. Whether LI-cadherin expression is also linked to the development and progression of malignant hematologic diseases is not known.
In this study, we for the first time showed that LI-cadherin can be detected in several leukemic B-cell lines like Raji, MHH, Nalm6, Z33, REH, and T-cell lines Jurkat, Molt3, Molt4, Molt16 by western bloting and RT-PCR. We subsequently analyzed the expression of LI-cadherin in leukemic bone marrow (BM) slide samples and correlated its impact on the clinical outcome in 119 children with first relapse acute lympnoblastic leukemia (ALL) enrolled in the Berlin-Frankfurt-Münster ALL relapse trial. LI-cadherin expression could be detected in 24 of 119 BM samples (20.2%) using immunofluorescence staining. The frequencies of LI-cadherin in B-cell progenitor (BCP)-ALL and pre-T/T-ALL were 18.4% (19/103) and 31.3% (5/16), respectively. Within BCP-ALL relapses, the maturation-linked expression of LI-cadherin was seen in 22.9% of more mature pre-B (n = 35) than in 17.2% of common (n = 64) or 0% of pro-B (n = 4) leukemic cells. Analysis was confined to BCP lineage to avoid biases related to immunophenotype. Most notably, the probability of survival (pSRV) at 5 years was significantly worse for children with first relapse BCP-ALL who expressed LI-cadherin in BM samples (n = 19) compared with patients who had no expression of LI-cadherin (n = 84) (pSRV: 0.71±0.06 vs. 0.35±0.17; p<0.05). Furthermore, the expression of LI-cadherin was also observed in BM stromal cells which are assumed to support leukemic cell growth and survival.
These results indicated that the expression of LI-cadherin in BM represents a negative prognostic factor for children with first relapse ALL. Since stromal cells also express LI-cadherin, they could bind to LI-cadherin expressing leukemic cells and thus modulate disease progression and/or response to therapy.
Determination of a HLA II Promiscuous Peptide Cocktail as Potential Vaccine Against EBV Latency II Malignancies.
Authors: Depil Stephane , Morales Olivier , Maillere Bernard , Delhem Nadira , Francois Violaine , Georges Bertrand , Morschhauser Franck , Auriault Claude , Pancre Veronique 
Published: October 2019

Abstract
The Epstein-Barr virus (EBV) is associated with several malignant diseases which can be distinguished by their patterns of viral latent gene expression. The latency II program is limited to the expression of the non-immunodominant antigens EBNA1, LMP1 and LMP2 and is seen in EBV-positive Hodgkin’s disease, nasopharyngeal carcinomas and peripheral T/NK-cell lymphomas. CD4+ T cells may play a crucial role in controlling these EBV latency II malignancies. The aim of this study was to determine a peptide cocktail containing highly promiscuous MHC class II epitopes derived from the EBV latency II antigens. Using the prediction software TEPITOPE, we selected 24 potential MHC II promiscuous peptides derived from the EBV latency II antigens EBNA1, LMP1 and LMP2. The predicted peptides were then submitted to peptide-binding assays on HLA II purified molecules, which allowed the selection of 6 peptides (EBNA1: 3; LMP1: 1; LMP2: 2) with a highly promiscuous capability of binding. This peptide cocktail was immunogenic in a model of HLA-DR1 transgenic mice, leading to a specific cellular and humoral Th1 response. To determine whether the peptides of the cocktail were recognized by human CD4+ T cells, we stimulated CD8-depleted PBMCs from 12 healthy EBV-seropositive donors expressing various HLA genotypes. A proliferative response was observed in all of the donors tested. Significant levels of IFN-gamma and IL-10 secretion were observed in 7/12 and 4/12 donors, respectively, using ELISA method. We also found a relatively low but significant number of IFN-gamma-secreting memory cells in 8 of the 10 donors tested using ELISPOT assay (range, 22 to 167 SFC per 106 CD8-depleted PBMCs). Finally, we analyzed by ELISPOT the responses obtained using PBMCs from 5 EBV-seropositive Hodgkin patients at different stages of the disease. No significant response was observed in the 2 patients at diagnosis. By contrast, a highly significant response was observed in a patient with EBV-associated Hodgkin lymphoma in remission.
In conclusion, we have determined an HLA II promiscuous peptide cocktail containing epitopes from EBV latency II antigens. This promiscuous peptide cocktail may be immunogenic in the majority of the population and could be used in immunotherapeutic approaches (as peptide-based vaccine or cellular therapy) against EBV latency II malignancies.
Anaemia Management in Patients on Peritoneal Dialysis in Portugal: A Nationwide Multicenter Survey.
Authors: Branco Patrícia Q. , Abreu Cristina P. , Pessegueiro Pedro , Amoedo Manuel , Rodrigues Anabela , Cabrita Antonio , Bruges Margarida , de Almeida Edgar , Prata Mateus Martins 
Published: October 2019

Abstract
Introduction: The European Best Practice Guidelines for the Anaemia Management (EBPG) recently published emerged as an international standard in the management of anemia in chronic kidney disease (CKD) patients.
Objectives: To evaluate the impact of theses guidelines in the clinical practice in Portugal.
Methods: This epidemiological, multicentric and cross-sectional study included patients on peritoneal dialysis that were under erythropoietin treatment in Portugal during 2004. Etiology of CKD, prevalence and anaemia treatment, comorbidity and side effects were evaluated.
Results: 220 patients from 5 Units were evaluated. Mean haemoglobin was 12.34 g/dL and only 13,2% of patients had haemoglobin <11 g/dL. Ninety-nine percent of patients were treated with erythropoietin: 65% with beta erythropoietin (beta) and 35% with darbepoetin alfa (darbe). Subcutaneous route had been used in all cases: 5,4% with once-monthly administration (darbe), 19,55 % two times monthly (darbe and beta), 59% with once a week regimen (darbe and beta), 11,55% in two weekly doses (beta) and 4,5% in three weekly administrations (beta). Doses requirements were different according to administration frequency. More than 85% of patients had haemoglobin > 11 g/dl and no significant difference in haemoglobin levels was achieved in the two groups (beta and darbe). Erythropoietin doses were greater in the group treated with darbe (127 versus 113 UI/kg/week), but inflammation markers were significantly higher as well diabetic patients in this group.
Conclusion: These results suggest that, according to the EBPG’s, mostly patients on PD in Portugal are already being well treated presenting heamoglobin levels in the therapeutic range.
The Involvement of Reactive Oxygen Species in Polyploidization of the M-07e Human Megakaryocytic Cell Line.
Authors: Côté Serge , Dussault Nathalie , Simard Carl 
Published: October 2019

Abstract
Hematopoietic cells mature in the bone marrow under the control of a diversity of growth factors and the influence of various cell types producing superoxide and other reactive oxygen species (ROS). As ROS may regulate activities of redox-sensitive enzymes implicated in a wide range of cellular processes, we have exposed the human megakaryocytic cell line M-07e to hydrogen peroxide (H2O2) at concentrations that increased intracellular ROS and examined whether expression of the megakaryocytic programme could be enhanced. The growth-factor dependent M-07e cells display surface markers characteristic of both early myeloid progenitors and more committed members of the magakaryocyte (Mk) lineage, such as glycoproteins GPIIb-IIIa (CD41) and GPIb (CD42). H2O2 significantly reduced cell proliferation without affecting viability. After 4 days of exposure to this reagent, expression of the early Mk marker CD41 was 1.2 times higher than that of control cells. Although no change in the expression of the late Mk marker CD42 was detected, exposure to H2O2 was found to increase the incidence of multinucleate cells, polyploidy and abnormal microtubule organising centre numbers. Investigation of this phenomenon on synchronized M-07e cells revealed that H2O2 arrested cytokinesis at a late stage and that some nuclei were still able to incorporate bromodeoxyuridine (BrdU). Cell division was similarly impaired when M-07e cells were either exposed to botulin toxin C3 transferase or Y-27362 inhibitor, suggesting that H2O2 treatments affected members of the Rho family of small GTP-binding proteins and/or their effectors. Together, these findings indicate that endoreplication in Mk may be linked to changes in the cellular redox state of these cells and support the concept that differentiation and polyploidization are independently regulated events.
Rituximab, Fludarabine, Mitoxantrone, and Dexamethasone (R-FND) for Relapsed Indolent Lymphomas (RIL).
Authors: Hagemeister F.B. , McLaughlin P. , Fayad L. , Samaniego F. , Dang N. , Goy A. , Romaguera J. , Pro B. , Beasley V. , Cabanillas F. , Rodriguez M. 
Published: October 2019

Abstract
Optimal therapy for patients (pt) with B-cell RIL remains controversial, and many treatment options include rituximab (R). Based on phase I–II studies of FND (fludarabine 25 mg/m2, d1–3; mitoxantrone 10 mg/m2, d1; dexamethasone 20 mg d1–5) treatment for RIL in which we observed a 48% CR rate, we studied the combination of R (375 mg/m2 d1) and FND for pt with RIL. Pt could not have received prior fludarabine, and were eligible if they had not previoiusly received R or had a response lasting at least 6 months (mo) to prior treament with R. Cycles were repeated every 4 weeks, and required an absolute neutrophil count of 1,000 and a platelet count of 100,000 to administer each cycle. Forty-two pt were entered onto this trial; however, one never received therapy after signing consent, and two were deemed ineligible after signing consent because of low cardiac ejection fractions (EF). All pt underwent biopsy prior to therapy; histologies included follicular gr1–3 in 30 pt, small lymphocytic in 7, marginal zone in 2. The median age was 58 (range 39–84) and median prior therapies 1 (range 1–3). The median number of cycles of R-FND delivered per patient was 6 (range 1–8). Of the 39 eligible and evaluable pt, 19 entered CR and 9 CRu for a CR/CRu rate of 72%, and 9 entered PR (23%) for an overall response rate of 95%. One had stable disease (SD), and one progression (PD). Eight underwent high dose therapy followed by autologous stem cell transplant (SCT) following a response to R-FND therapy. Five of these had achieved CR/CRu with R-FND after 1–6 cycles, and 3 PR after 2–6 cycles. In all, 14 of the 37 responders to R-FND (37%) have had progression; however, none of the 8 who underwent SCT has had progression, nor has the one with SD. In, 24 (62%) still remain free of progression with a median follow-up for living pt of 32 mo. In all, 6 pt have died of PD, including 4 who were ineligible for or refused SCT. The 2-year failure-free survival (FFS) and overall survival (OS) results for all pt are 66% and 90%. The 2-year FFS for responders is 66%, and the 2-year OS for all pt, with pt undergoing SCT censored at time of SCT is 81%. As expected, the main toxicity following R-FND was hematologic: gr 4 neutropenia occurred in 15 pt and in 15 of 130 cycles for which information is available, and gr 3–4 thrombocytopenia in 5 pt and in 6 cycles. In all, 13 of the 28 responders received less than 6 cycles of therapy; reasons included prolonged thrombocytopenia in 4, early SCT in 6, asymptomatic decrease in EF in one, and physician’s choice in 2. No patients died of acute toxicity while receiving R-FND. We conclude that 1) R-FND is a very active and well tolerated regimen for relapsed indolent lymphomas 2) Results appear very favorable compared to prior studies with FND 3) In this population, patients receiving R-FND were able to undergo SCT, and had very favorable outcomes.
Immune Tolerance Induction by High Doses FVIII in Hemophilia A Patients with Inhibitor Does Not Require Deletion of FVIII-Specific T Cells.
Authors: Jacquemin Marc G. , Lavend’homme Renaud , Tinot Thérèse , Peerlinck Kathelijne , Saint-Remy Jean Marie , Pautard Brigitte 
Published: October 2019

Abstract
In patients with hemophilia A and FVIII inhibitor, tolerance to FVIII can frequently be restored by prolonged administration of FVIII (immune tolerance induction). We studied the cellular response to FVIII in two patients successfully desensitized with high doses of FVIII. Each patient had also transiently received glucocorticoids, when the antibody titer increased after an initial decline upon start of the desensitization. On repeated stimulations with FVIII loaded autologous dendritic cells, FVIII-specific T oligoclonal cell lines and T cell clones were derived from one of the two patients up to two years after complete elimination of the inhibitor. The interleukins produced by the T cell lines included IL-2, IL-5 and IL-13. Although ITI is frequently unsuccessful in mild/moderate haemophilia A patients, this patient remained tolerant to FVIII even after a 10 days FVIII continuous infusion, 18 months after complete elimination of the inhibitor. Several microcultures from CD4+ T cells purified after this treatment responded to FVIII specifically demonstrating the long term persistence of FVIII-specific T cells after ITI. By contrast, no FVIII-specific T cell lines could be derived from blood of control individuals without hemophilia A. Thus, although in animal models of tolerance, administration of high doses of antigen result in T cell elimination, deletion of FVIII-specific T cells is not required for successful tolerance induction to FVIII.
The Concentration of Exogenously Added Lipids and Endogenously Available Microparticles Are Major Determinants of Thrombin Generation in Plasma.
Authors: Kluft C. , Meijer P. , Kret R. , Kaufmann V. , Mager J. 
Published: October 2019

Abstract
Thrombin generation tests are started by adding coagulation activator (e.g. tissue factor or contact activator) together with lipids.
We evaluated the role of lipids in tests started with a fixed amount of tissue factor (7.16 pM) and addition of either 3.2 (high) or 0.32 (low) μM of lipids (Technothrombin ® TGA assays from Technoclone, Vienna) in both normal plasma and plasma that was ultracentrifuged (30 minutes at 15,000 g) to remove microparticles (MPs). The tests were performed in plasma samples of groups of apparently healthy individuals.
It was observed in 54 healthy volunteers that starting with high or low lipids substantially influenced the total amount of thrombin generated expressed by the area under the curve (AUC) (AUC median 2492, IQR 716 versus AUC median 1154, IQR 652 nM*min, respectively), the rate of thrombin formation or velocity index (VI) (median 53.4, IQR 43.6 and median 11.7, IQR 10.6 nM/min, respectively), and the lag time to the start of thrombin generation (median 10.3, IQR 2.4 versus median 17.5, IQR 5.0 minutes, respectively). It can be concluded that the VI is the most sensitive variable showing approximately a factor of 5 difference between high and low lipid.
The difference of adding high or low lipid on VI was primarily dependent upon the lipid concentration and to a limited extend influenced (univariate) by factor II levels (12%) and factor IX levels (10 %), taking into account practically all known coagulation factors (fibrinogen, II, V, VII, VIII, IX, X, XI, XII, PC, PS, PZ, TFPI, PCI) determined in the 54 plasma’s as potential determinant. In plasma of 36 volunteers microparticles were removed and VI dropped to 19% in comparison to the untreated plasma when tested with the addition of high lipid and to 3.1% with the addition of low lipid. Re-addition of MPs to a specific plasma restored VI dose dependently with an optimum at 2x104 MPs/ml. The same level of VI (63.8 and 62.0 nM/min, respectively) was reached with high and low lipid addition when 2.104 MPs/ml were added.
It is concluded that endogenous MPs play an important role in thrombin generation tests, in particular but not exclusively when the test is performed with low levels of added lipids.
Metabolic Analysis of Bone Marrow Mesenchymal Stem Cells and Adipose-Derived Stem Cells Using NMR-Based Metabolomics.
Authors: Ogawa Rei , Fujimura Juri , Hirakawa Keiko , Uekusa Kyoko , Yuta Kohtaro , Mizuno Hiroshi , Ohno Youkichi , Hyakusoku Hiko 
Published: October 2019

Abstract
Background: Nuclear magnetic resonance (NMR) -based metabolomics has been suggested to be useful for exhaustive analysis of metabolic pathways of cells or tissues. We report our study on bone marrow mesenchymal stem cells (BSCs) and adipose-derived stem cells (ASCs) using NMR-based metabolomics.
Materials and Methods: Five-week-old Wister rats were used for this study. BSCs were harvested from the femur, ASCs from inguinal fat pads, and control fibroblasts from the abdominal dermis. The cells were cultured in DMEM with 10% fetal bovine serum and harvested after two passages of the subculture. Then, the cells were subjected to freezing in liquid nitrogen and crushed to extract the aqueous metabolites. 1H-NMR spectra was measured and analyzed by a computer software (Alice2 for metabolome™ and ADMEWORKS/ModelbuilderTM).
Results: BSCs, ASCs and fibroblasts were clearly separated into three groups on a principal component analysis (PCA) plot.
Conclusion: ASCs, BSCs and fibroblasts were considered to have different metabolic activities, and NMR-based metabolomics will henceforth be useful for the detection, analysis, and characterization of various kinds of stem cells.
Thrombelastographic Observations on the Characteristics of Hemophilic, Thrombocytopenic and Heparinized Blood
Authors: DE NICOLA PIETRO , MAZZETTI G. M. 
Published: October 2019

Abstract
1. Thrombelastographic determinations were made in cases of AHG-, PTC- and PTA-deficiencies, in thrombocytopenias and in normal plasmas after the addition, in vitro, of heparin and synthetic heparin-like substances.
2. The components of the thrombelastogram (TEG) were correlated with respect to the reaction time (r), the rate of clot formations (k), and the maximal amplitude (ma).
3. The differentiation of the hemophilic and thrombocytopenic syndromes was made on the basis of the typical variations of r, k and ma: prolonged r and k in hemophilia, prolonged k and decreased ma in thrombocytopenias.
4. The behavior of heparinized blood was characterized by a hemophilia-like prolongation of r and k and a thrombocytopenic-like decrease of ma, with variations depending on the compound used.
5. The correlations between the r, k and ma values of TEG are suggested for the evaluation of thrombelastography.
The Effects of Varying Concentrations of Human Platelets and Their Stored Derivatives on the Recalcification Time of Plasma
Authors: KLEIN EDMUND , FARBER SIDNEY , FREEMAN GUSTAVE , FIORENTINO ROSEMARY 
Published: October 2019

Abstract
Human platelets and their stored, frozen and lyophilized derivatives do not excessively promote coagulation, as indicated by the calcium clotting time. High concentrations of platelet material inhibit coagulation, while dilution to physiologic levels returns the recalcification time to normal values.
The Effects of Various EDTA Complexes on Coagulation
Authors: LEIKIN SANFORD , BESSMAN SAMUEL P. 
Published: October 2019

Abstract
The one-stage prothrombin time of oxalated plasma was prolonged on incubation with disodium EDTA. This was due to the destruction of Ac-Globulin or the inhibition of its production from a precursor stage. There was a similar change with disodium calcium EDTA, indicating some metal other than calcium was probably being chelated.
A marked prolongation of the prothrombin time of oxalated plasma occurred on incubation with cupric, ferrous, stannous, cobaltous, and magnesium EDTA, but manganous, zinc and nickel EDTA produced no prolongation of the prothrombin time. This would support the concept that a metal ion may be concerned with the maintenance of Ac-Globulin or its conversion into an active form.
The cobaltous, cupric, ferrous and ferric ions produced a prolongation of the prothrombin time. This effect was corrected by the use of prothrombin free plasma except in the case of cobalt. The manganous, barium and nickel ions did not prolong the prothrombin time and nickel was effective in maintaining the prothrombin time at its original level. Its most effective concentration was .001 M. At higher concentrations it produced a prolongation which was not corrected by the addition of prothrombin-free plasma.