bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nitrated Lipids in a Murine Model of Sickle Cell Disease at Baseline.
Authors: Schwartz Jeffrey , Baker Paul R.S. , Schopfer Francisco J. , Freeman Bruce A. 
Published: October 2019

Abstract
Introduction
Sickle cell disease (SCD) is increasingly recognized as a disorder of inflammatory homeostasis. One major focus in recent years has been understanding the role of Nitric Oxide (NO) in the pathophysiology of SCD. NO is a critical mediator of inflammatory pathways and current evidence supports the precept that NO bioavailability is decreased in SCD, resulting in normal concentrations of NO at baseline but an inability to increase NO during stress. Nitrated fatty acids, such as Nitrolinoleate (LNO2), have recently been reported as potent and abundant anti-inflammatory signaling mediators with the ability to cause vasorelaxation and inhibition of platelet and neutrophil activation. Evidence supports their anti-inflammatory signaling is mediated through the release of NO and NO-related products. LNO2 has not previously been described in patients with SCD and our objective was to quantify LNO2 in a murine model of SCD at baseline.
Methods
Whole blood was obtained from transgenic sickle cell and wild type mice (n = 5 and 6, respectively). Blood was centrifuged and separated into plasma and packed red blood cells (RBCs). These biological samples were prepared for lipid analysis by the method of Bligh and Dyer; care was taken so that the pH of the extraction milieu was consistently maintained at 7 so as to avoid artifactual nitration. Samples were analyzed for free LNO2 content by electrospray ionization tandem mass spectrometry. Using a hybrid triple quadrupole ion trap mass spectrometer, MRM transitions were monitored that specifically identified nitrated linoleic acid species; these species were concomitantly confirmed by the qualitative analytical abilities of the ion trap. The presence of nitrated linoleic acid was confirmed by HPLC chromatographic retention times, MS/MS “fingerprints” and was quantitated by the inclusion of a known quantity of 13C-labeled LNO2.
Results
LNO2 concentration was calculated as a function of the ratio of analyte to internal standard peak areas by using an internal standard curve linear over five orders of magnitude. Free LNO2 in the RBCs and plasma of 5 transgenic sickle cell mice were 3.97 ± 2.56 nM and 12.37 ± 9.83 nM, respectively. Free LNO2 in the RBCs and plasma of 6 wild type mice were 9.49 ± 8.32 nM and 14.91 ± 10.08 nM, respectively. There were no significant differences in LNO2 concentration between any of the groups.
Conclusions
LNO2 is present in both transgenic sickle cell mice and wild type mice in comparable concentrations at baseline. As a mediator of NO anti-inflammatory signaling, this is consistent with human studies showing comparable concentrations of NO metabolites at baseline between sickle cell patients and healthy controls. Further study of LNO2 in sickle cell disease is warranted to better understand its role in the inflammatory process associated with acute stress, such as vaso-occlusive pain crisis and acute chest syndrome, when NO bioavailability is decreased.
The Outcomes of Preimplantation Genetic Diagnosis Therapy in Treatment of β Thalassemia - a Retrospective Analysis.
Authors: Qureshi Naveen , Foote Drucilla , Madore Rebecca , Walters Mark C. , Singer Sylvia Titi , Quirolo Keith C. , Vichinsky Elliott P. 
Published: October 2019

Abstract
BACKGROUND: β thalassemia is one of the most common single gene disorders. Hematopoietic stem cell transplantation (HCT) from a human leukocyte antigen (HLA)-identical sibling donor is a curative option that minimizes the risk of graft-versus-host disease, compared to alternative donor HCT. In families that have an affected child, preimplantation genetic diagnosis (PGD) can be utilized to select an unaffected embryo that is HLA-identical. Briefly, this procedure requires in vitro fertilization, oocyte retrieval, fertilization and blastomere biopsy for preimplantation analysis and identification of unaffected HLA-identical embryos. After delivery, umbilical cord blood from the sibling donor is collected for HCT. In our institution, PGD has been pursued as a therapeutic option by families with thalassemia. The estimated cost of this uninsured procedure is $20,000 per cycle.
METHODS: Families affected with β thalassemia who attempted PGD were identified and reviewed for indication, attempted cycles, successful pregnancy and transplantation outcome.
RESULTS: Eight identified families affected by thalassemia underwent PGD. The diagnosis of their affected children included: 6 cases of β thalassemia major and 2 cases of transfusion dependent E β thalassemia patients. A total of 14 cycles of PGD were attempted, ranging from 1–4 attempts per family. Following successful identification of HLA-identical cells, 2 pregnancies occurred (1 early miscarriage, 1 successful delivery). This pregnancy resulted in the engraftment of a β thalassemia child.
CONCLUSION: PGD including selection of HLA-identical sibling embryos is a novel, therapeutic approach for patients with β thalassemia. While this offers the possibility of recruiting a suitable donor for HCT, it is limited by significant financial and emotional burdens that it places on families affected with β thalassemia. Improvements in its efficiency and cost will make this a more viable option for affected families.
Quality of Life in Patients with Thalassemia.
Authors: Pakbaz Zahra , Treadwell Marsha , Yamashita2 Robert , Foote Drucilla , Vichinsky Elliott 
Published: October 2019

Abstract
Introduction: Thalassemia patients have experienced a dramatic increase in lifespan secondary to improved and more complicated therapy. The impact of the disease and its treatment on quality of life is largely unknown. Determining the degree of health impairment as perceived by the patient is essential information needed to recommend suitable therapy. Factors that affect the quality of life of thalassemia major patients may differ from thalassemia intermedia patients. Identifying the specific causes for negative patient assessment of overall health status can result in successful intervention. The objective of this study is to determine the factors that affect quality of life in both transfused and non-transfused thalassemia patients.
Methods: The Dartmouth Care Cooperative Chart System (COOP) questionnaire is a standardized, validated, visual screening tool that screens the major domains affecting quality of life. Patients rate quality of life from excellent (1) to poor (5). Scores of 1 and 2 are normal. A Score of 3 are mild to moderate impairment, and 4 and 5 are severe abnormalities. 50 patients were randomly selected during a comprehensive visit to complete a COOP questionnaire. These results were augmented by a brief medical history and chart review.
Results: Forty-eight thalassemia patients, including 25 transfusion dependent (Tx) and 23 non-transfused (Non-Tx) patients (50% female) were randomly selected and completed the COOP questionnaire. The mean age of the total population was 19 years (0.9–37.9 yrs) and was similar in both groups. Half of both groups had scores of 3 or less indicating no severe impairment. However, 56% of patients had ratings of 3 indicating mild to moderate impairment of major domains. Four patients (2 Tx, 2 Non-Tx) had repeated 4–5 ratings in multiple domains indicating severe impairment of quality of life. The most commonly reported affected domains were feelings, such as anxiety, depression, and concern of overall health status or indications of recent deterioration in health.
Conclusion: At least 50% of transfusion and non-transfusion dependent thalassemia patients demonstrate some impairment in quality of life. Forty-four percent of the population had a severe impairment in at least one domain. In particular, mental health issues are widespread. In contrast to previous beliefs, non-transfusion dependent patients also suffer serious impairment in quality of life. This data suggests all patients should undergo quality of life assessments and intervention, which focuses on affected domains. Studies to determine if quality of life affects patients’ adherence to chelation therapy are needed.
Plasma Gelatinolytic Activity in Leukemias.
Authors: Wrzyszcz Aneta , Urbaniak Joanna , Wrobel Tomasz , Mazur Grzegorz , Tomaszewska-Toporska Beata , Kuliczkowski Kazimierz , Wozniak Mieczyslaw 
Published: October 2019

Abstract
Gelatinase A (Matrix Metalloproteinase 2, MMP-2) and B (Matrix Metalloproteinase 9, MMP-9) are secreted by connective tissue, endothelial, epithelial and hematopoietic cells. Elastase and gelatinases produced by granulocytes are released in whole blood in response to varied stimuli. They induce breakdown of connective tissue and play an important role in processes of cell transmigration and tissue remodeling. The aims of this study were to determine and compare the plasma concentration of PMN elastase and the gelatinase activity in patients with chronic myelogenous leukemia (CML, n=16), acute myeloblastic leukemia, AML, n=53 and acute lymphoblastic leukemia, ALL, n=18) and in healthy persons (n=22). We measured activity of MMP-2 and MMP-9 using gelatine zymography and concentration of elastase from polymorphonuclear leukocytes (PMN) in complex with alpha1-proteinase inhibitor using ELISA. The MMP-9 activity in plasma from patients with CML was higher than that from AML, ALL and reference groups. The MMP-9 activity in AML and ALL group was lower than in healthy persons. There was no significant difference in the MMP-2 levels between the plasma samples from patients with CML or ALL and those from healthy subjects, but MMP-2 activity was lower in the reference group than in AML. PMN elastase concentration in plasma from the healthy reference group was lower than that from CML and AML patients. Furthermore, PMN elastase concentration in plasma from CML patients was higher than that from AML and ALL. We found significant correlation between MMP-9 activity and white blood cells count in the reference group (r=0,56), CML group (r=0,70) and AML group (r=0,44). The PMN elastase concentration increased proportionally to the white blood-cell count (r=0,51) in plasma from patients with CML only. There was significant relationship between the count of granulocytes in different stages of maturation with PMN elastase and MMP-9 activity: promyelocytes (r=0,73 for elastase and r=0,75 for MMP-9), myelocytes (r=0,63 and r=0,79), metamyelocytes (r=0,56 and r=0,83), band neutrophils (r=0,64 and r=0,74), segmented neutrophils (r=0,73 for MMP-9) and eosinophils (r=0,64 for MMP-9) in blood from CML patients. Increased MMP-9 activity was correlated with increased MMP-2 activity in the reference group (r=0,58) and AML group (r=0,50), however it was correlated with decreased MMP-2 activity in the CML group (r=−0,59). In the CML group it was observed that decreased MMP-2 activity correlated with an increased count of: blasts (r=−0,64), promyelocytes (r=−0,77), myelocytes (r=−0,63), metamyelocytes (r=−0,64) and band neutrophils (r=−0,60). Gelatin zymography can be employed to display differences of plasma MMP-2 and MMP-9 activity between patients with chronic myelogenous leukemia, acute leukemia and healthy persons.
Evaluation of the Usefulness of Detected Platelet Antibodies for the Prognosis of Treatment Results in Patients with Thrombocytopenic Purpura.
Authors: Sikorska Anna , Maslanka Krystyna , Konopka Lech , Zupanska Barbara 
Published: October 2019

Abstract
Platelet antibodies are the main cause of platelet destruction in immunological thrombocytopenic purpura. However, the significance of their detection for prognosis of treatment results in ITP patients (idiopathic immune thrombocytopenic purpura) has not yet been determined.
The aim of this work was to evaluate the effectiveness of treatment with corticosteroids, splenectomy and immnunosupressive drugs of 409 ITP patients in relation to the detection of platelet antibodies.
Platelet antibodies were determined in the ITP patients under observation:
in connection with autologous platelets - with platelet immunofluorescence test (PIFT),
in serum - with immunoenzimatic test using monoclonal antibodies directed at GPII/IIIa, GPIb, GPIa/IIa (MAIPA - monoclonal antibody immobilization of platelet antigens).
In treatment effectiveness prognosis the multifactor statistical analysis was used involving not only platelet antibodies but also other parameters such as age, sex, course of disease, megacariocyte count in bone marrow. In patients after splenectomy -the spleen-liver index and the time lapse between ITP diagnosis and surgical procedure were additionally taken into account.
The statistical analysis revealed that platelet antibodies had no significant effect on the treatment results prognosis in ITP patients. However, while analysing groups of patients with different treatment administered, it was found that the effect of platelet antibodies on positive prognosis treatment was significant though not very big effect in the case of patients treated with corticosteroids and immunosuppressive drugs while nonsignificant in the case of patients after splenectomy.
Additional factors significantly effecting positive treatment prognosis in all patients were: severe/acute course of disease, increased/normal megacariocyte count, young age, female sex. In splenectomy patients the spleen-liver index (up to 5.7:1) seems to be a significantly beneficial factor as well as the time lapse between diagnosis and procedure (up to 9 years since diagnosis).
Functions of Thrombin Receptors in the Reversible Distribution of Platelet Glycoprotein Ib within Activated Platelets.
Authors: Yue Han , Pasquet Jean-Max , Nurden Alan , Changgeng Ruan 
Published: October 2019

Abstract
Platelets are critical in normal haemostasis and arterial thrombosis. As a potent activator, thrombin activates human platelets by cleavage of the protease-activated receptors PARs, exposing new amino terminus which serve as tethered peptide ligands, binding to the receptors induce transmembrane signaling. Thrombin also binds to platelet glycoprotein Ib, whose redistribution within platelet was showed to be reversible upon to thrombin or to PAR1 and PAR4 peptides. In an attempt to understand the reversible expression of platelet GPIb and cytoskeleton reorganization during platelet activation, then determine functions of thrombin receptors in GPIb redistribution. we used peptide SFLLRNPNDKYEPF (PAR1-AP, trap) and AYPGKF (PAR4-AP) for stimulating platelet at different time points (0~60minute), detected the platelet surface GPIbα and P-selectin with flowcytometry, and compared the alteration of GPIbα, actin and myosin in cytoskeleton by western-blot, then analyzed the membrane cytoskeleton followed by GPIbα immunoprecipitation.
As expected, a reversible interalisation of GPIbα was obtained by PAR1 or PAR4 activation, and a transient change of actin, myosin and GPIbα /myosin GPIbα /actin association were also found in this course. These transient internalisations were apparently blocked by Cytochalasin D (inhibitor of actin polymerisation) or BAPTA/AM (calcium chelator). At the same time, ApyraseVII had weak effect on GPIbα interalisation, although the return of GPIbα to platelet surface was accelerated by this low ATP/ADPase, which quickened GPIbα dissappearance in cytoskeleton and the dissociation of GPIb/myosin or GPIb/actin during PAR1-AP activation.100nM and 10μM wortmannin were used to inhibit phosphatidylinositol 3-kinase (PI3-K) and/or myosin light chain kinase (MLCK) in our experiments. In response to both PARs activation, GPIbα interalisation was partly inhibited by 100nM wortmannin but little change for 10μM wortmannin, and a delayed restoration of surface GPIbα was observed in the presence of 10μM wortmannin upon PAR1-AP activation.. Apart from the above reagents, Ro-31-2220 (inhibitor of protein kinase C) induced a decreased GPIbα centralisation in response to PAR1 activation, and blocked the pool of GPIbα inside platelet in the latter course of PAR4 activation (p<0.05 at 10,30 min). Globally, Our study confirmed that thrombin receptors are important for platelet signal transmission, Stimulation of either receptor is sufficient to trigger platelet activation and induce GP Ib redistribution, which is correlated with cytoskeleton reorganisation, depending on the actin polymerisation and calcium mobilisation and implicate both myosin and actin. Our results also suggested critical roles of ADP, PI3-K or protein kinase C (PKC) in the GPIb redistribution.
Higher Risk of Ischemic Stroke Associated with Factor XI Levels in Dyslipidemic Patients.
Authors: Santamaria Maria Amparo , Oliver Arturo , Mateo Jose , Belvis Roberto , Marti-Fabregas Joan , Souto Juan C. , Urrutia Teresa , Cristina Vallve , Borrell Montse , Fontcuberta Jordi 
Published: October 2019

Abstract
Ischemic stroke (IS) is a complex disease that involves genetic and environmental factors. The role of Factor XI in arterial thrombosis including IS is unclear. We have investigated the risk of IS related to Factor XI levels in a case-control study. We studied 445 individuals: 218 diagnosed with IS and 227 age-gender-ethnic control subjects. We measured Factor VIIIc, fibrinogen and Factor XIc levels. Factor XI<144% was taken as the reference group in the statistical analysis. Basic characteristic of patients and controls are summarized in the Table 1.
When we analyzed the OR in all population, we observed an interaction between dyslipidemia and high FXI levels. So, we analyzed the data in 2 subgroups, dyslipidemic and non-dyslipidemic. The crude OR of IS in dyslipidemic patients with high levels of FXI was 4.2 (95% CI:1.2–14.8) compared with dyslipidemic controls and low levels of FXI, but the OR in the non-dyslipidemic with high levels of FXI subgroup was 1.2 (95% CI: 0.4–3.2). The adjusted OR of IS in dyslipidemic patients with high levels of FXI was 6.4 (95%CI: 1.6–26.1) compared with dyslipidemic controls, but the OR in non-dyslipidemic subgroup with high levels of FXI was 0.6 (95%CI: 0.2–2.1). In conclusion, we found almost a six-fold higher risk of IS in patients with dyslipidemia and high levels of FXI. Further studies should elucidate the role of Factor XI in IS and therapeutical approaches should become apparent in regard to patients with dyslipidemia and high Factor XI plasma levels.
Table 1.
IS (n=218)n (% ) Controls (n=227)n (% ) Unadjusted OR (95% CI) *Difference statistically significant (p<0.059 after adjustment by sex and age Sex (F/M) 104/114 108/119 NS Age (years, mean, range) 57 (23–80) 55(21–80) NS Smoking 94(45) 75(40) 1.6(1.1–2.3)* Dyslipidemia 91(42) 40(18) 3.4(2.2–5.2)* Family History of arterial thrombosis 112(51.7) 39(19) 5.1(3.3–7.8)* Hypertension 96(43.9) 39(17.3) 3.7(2.4–5.8)* Morbid Obesity 12(4.4) 6(2.6) 2.6(0.9–7.5) Alcohol Intake 20(9.2) 11(4.8) 1.9(0.9–4.2) Diabetes Mellitus 41(19) 12(5) 4.2(2.1–8.2)* Factor VIIIc(%, mean, range) 187.3(62–516) 157.1(48–360) p<0.0001 Fibrinogen (g/l)(mean, range) 3.7(1.9–8.4) 3.5(2.1–7.8) p<0.002
The Risk of Thrombosis in Patients with Lupus Anticoagulants Is Predicted by Specific Antibody Profiles.
Authors: Huh Hee Jin , Chi Hyun Sook , Young Mi , Jang Sung Soo , Park Chan Jeoung 
Published: October 2019

Abstract
Introduction: Lupus anticoagulants(LA) are immunoglobulins which inhibit phospholipid dependent coagulation tests and associated with thromboembolic event. The autoantibodies that cause Lupus anticoagulant activity are heterogeneous but predominantly directed against β-2-glycoprotein(β2GPI) or prothrombin. The purpose of this study was to evaluate the prevalence of IgG, IgM anti-cardiolipin antibody(ACA), anti-β2GPI antibody and anti-prothrombin antibody in patient with lupus anticoagulant activity, and to predict the risk of thromboembolic event in patients with different immunologic profile.
Materials and methods: Lupus anticoagulant positive plasma samples from 163 patients which were sent us under the impression of antiphospholipid antibody syndrome were selected. The activity of LA was detected by mixing test and simplified DRVVT test (Gradipore Ltd, Sydney, Australia). IgG, IgM ACA (Inova Diagnostics, Sandiego, CA, USA), anti-β2GPI antibody and anti-prothrombin antibody (BL-Diagnosika, Gmbh, Mainz, Germany) were measured by commercial enzyme linked immunoassay (ELISA). The 163 patients divided into nine groups according to the results of ELISA for evaluation of correlation with thromobosis.
Results: A history of 1 or more thromboembolic events was found in 49 patients (30.1%): venous thrombosis in 29 patients (17.8%), arterial thrombosis in 29 patiensts (17.8%) and recurrent events in 14 patients (8.6%). The positivity of ELISA was follows; IgG ACA, 14 cases (8.6%); IgM ACA, 24 cases (14.7%); IgG and IgM ACA, 3 cases (3.7%); IgG anti-β2GPI antibody, 10 cases (6.1%); IgM anti-β2GPI antibody, 5 cases (3.1%); IgG and IgM anti-β2GPI antibody, 3 cases (1.8%); IgG anti- prothrombin antibody, 48 cases (29.4%); IgM anti-prothrombin antibody, 22 cases (13.5%); IgG and IgM anti-prothrombin antibody 10 cases (6.1%). Venous thrombosis prevalence was elevated in 6(25.0%) of 24 patients with IgM ACA and 1(20%) of 5 patients with IgM anti-β2GPI antibody. Arterial thrombosis prevalence was elevated in 3(30.0%) of 10 patients with IgG anti-β2GPI antibody and 5(22.7%) of 22 patients with IgM anti-prothrombin antibody. The univariate logistic analysis of risk factors for thrombosis indicated that of IgM ACA and IgM anti-β2GPI antibody were risk factors for venous thrombosis (Odds ratio, 2.3; 95% confidence interval 0.7–7.3, OR, 2.3; 95% CI 0.1–40.5) and IgG anti-β2GPI antibody were risk factors for arterial thrombosis and recurrent events (OR, 6.3; 95%CI 0.9–46.2, OR, 5.9; 95%CI 0.4–80.4).
Conclusion: The anti-prothrombin antibody is more frequently detected in patients with LA activity than anti-β2GPI antibody. However, anti-β2GPI antibody test is more helpful to identify LA positive patients at risk of thrombosis.