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March 15, 2018: Blood
Yogesh Patil, Panayiotis Bilalis, Georgios Polymeropoulos, Sarah R Almahdali, Nikos Hadjichristidis, Valentin O Rodionov
A well-defined amphiphilic miktoarm polymer incorporating poly(vinylidene fluoride) (PVDF), polystyrene (PS), and poly(ethylene glycol) (PEG) blocks was synthesized via a combination of atom-transfer radical polymerization (ATRP), iodine transfer radical polymerization (ITP), and copper-catalyzed azide-alkyne cycloaddition (CuAAC). Morphology and self-assembly of this star polymer were examined in organic solvents and in water. The aggregates formed in water were found to possess unusual frustrated topology due to immiscibility of PS and PVDF...
March 15, 2018: Molecular Pharmaceutics
Honar Cherif, Andreas Greinacher, Norbert Lubenow
We report on a patient with inherited macrothrombocytopenia, MYH9 related disease (MYH9-RD). The patient was wrongly diagnosed and repeatedly treated for immune thrombocytopenia (ITP) for nearly 50 years. Cases of misdiagnosed MYH9-RD and other hereditary thrombocytopenias have been described previously. Typical clinical features such as renal failure and/or progressive loss of hearing should give grounds to suspect hereditary thrombocytopenia. Initial laboratory diagnosis can start with a simple blood smear followed by immunohistochemistry and genotyping...
March 13, 2018: Läkartidningen
Ishac Nazy, John G Kelton, Jane C Moore, Rumi Clare, Peter Horsewood, James W Smith, Nikola Ivetic, Vanessa D'Souza, Na Li, Donald M Arnold
Autoantibodies to thrombopoietin (TPO, also termed THPO) or the TPO receptor (cMpl, also termed MPL) could play a pathological role in immune thrombocytopenia (ITP). In this study, we tested for autoantibodies against TPO, cMpl, or the TPO/cMpl complex in ITP and other thrombocytopenic disorders. Using an inhibition step with excess TPO in fluid-phase to improve binding specificity, the prevalence of anti-TPO autoantibodies was: active ITP: 9/32 (28%); remission ITP: 0/14 (0%); non-immune thrombocytopenias: 1/10 (10%); and healthy controls: 1/11 (9%)...
March 13, 2018: British Journal of Haematology
Yuria Shinohara, Mitsutoshi Tsukimoto
Damaged tissues and cells release intracellular purine nucleotides, which serve as intercellular signaling factors. We previously showed that exogenously added adenine nucleotide (250 μM ATP) suppressed the activation of murine splenic T lymphocytes. Here, we examined the effects of other purine nucleotides/nucleosides on mouse T cell activation. First, we found that pretreatment of mouse spleen T cells with 250 μM GTP, GDP, GMP, guanosine, ITP, IDP, IMP or inosine significantly reduced the release of stimulus-inducible cytokine IL-2...
March 7, 2018: Biochemical and Biophysical Research Communications
Shu-Ruei Wu, Hsiao-Ching Kuo, Wei-Chun Huang, Yung-Feng Huang, Yee-Hsuan Chiou, Yu-Hsiang Chang, Bao-Ren Nong
INTRODUCTION: Immune thrombocytopenia (ITP) is an immune-mediated disease; it has been reported to be associated with several diseases. The data on ITP in patients with hepatitis B, tuberculosis, or thyroid diseases are relatively scarce. In addition, these diseases are not rare in Taiwan, together with hepatitis C and Helicobacter pylori which are also related to ITP. METHODS AND MATERIALS: We identified 1223 ITP patients and characterized these patients between 2000 and 2013 from the National Health Insurance Research Database...
March 2, 2018: Thrombosis Research
Alexandra Schifferli, Andreas Holbro, Meera Chitlur, Michael Coslovsky, Paul Imbach, Hugo Donato, Mohsen Elalfy, Elena Graciela, John Grainger, Susanne Holzhauer, Cecilia Riccheri, Francesco Rodeghiero, Marco Ruggeri, Hannah Tamary, Tatjana Uglova, Runhui Wu, Thomas Kühne
Comparative clinical studies of children and adults with immune thrombocytopenia (ITP) are poorly covered in the literature. However, the accepted classification of ITP -childhood ITP and adult ITP-results in considerable differences in treatment protocols and practice guidelines. The analysis of the Pediatric and Adult Registry on Chronic ITP (PARC-ITP) of patients at first presentation demonstrated fewer differences in clinical and laboratory findings at initial diagnosis between children and adults than expected...
March 8, 2018: American Journal of Hematology
Xia Shao, Boting Wu, Luya Cheng, Feng Li, Yanxia Zhan, Chanjuan Liu, Lili Ji, Zhihui Min, Yang Ke, Lihua Sun, Hao Chen, Yunfeng Cheng
BACKGROUND: Although impaired myeloid-derived suppressor cells (MDSCs) recently have been studied in immune thrombocytopenia (ITP), another myeloid-derived cell population signified as M2 macrophages has not been investigated properly in ITP patients. In the present study, we intended to determine the features of circulating M2-like macrophages, to examine its relationship with MDSCs, and to explore their prognostic values in ITP. METHODS: Peripheral blood mononuclear cells from healthy controls and primary ITP patients were isolated to test the circulating M2-like macrophages and MDSCs...
March 2, 2018: Journal of Translational Medicine
Taylor Olmsted Kim, Jenny Despotovic, Michele P Lambert
Eltrombopag is currently the only US Food and Drug Administration-approved thrombopoietin receptor agonist for the treatment of chronic immune thrombocytopenia (ITP) in children. This oral, once-per-day therapy has shown favorable efficacy and adverse effect profiles in children. Two multicenter, double-blind, placebo controlled clinical trials (PETIT [Efficacy and Safety Study of Eltrombopag in Pediatric Patients With Thrombocytopenia From Chronic Idiopathic Thrombocytopenic Purpura (ITP)] and PETIT2 [Study of a New Medication for Childhood Chronic Immune Thrombocytopenia (ITP), a Blood Disorder of Low Platelet Counts That Can Lead to Bruising Easily, Bleeding Gums, and/or Bleeding Inside the Body]) demonstrated efficacy in raising platelet counts, reducing bleeding, and reducing the need for concomitant ITP therapies with relatively few adverse effects...
February 27, 2018: Blood Advances
Dorota Radkowiak, Anna Zychowicz, Anna Lasek, Michał Wysocki, Piotr Major, Michał Pędziwiatr, Piotr Budzyński, Jan Kulawik, Andrzej Budzyński
BACKGROUND: Laparoscopic splenectomy (LS) has become the gold standard in elective spleen surgery. Although it is considered relatively safe, treatment results vary depending on a hospital's profile and the experience of the surgeon and center. We would like to present experience of a high-volume referral center with minimally invasive operations of the spleen. MATERIAL AND METHODS: The retrospective cohort study included consecutive patients undergoing laparoscopic splenectomy in tertiary referral surgical center in 1998-2017...
February 23, 2018: International Journal of Surgery
Francesco Rodeghiero
In primary chronic immune thrombocytopenia, long-term response to splenectomy, with 60% of patients enjoying a treatment-free life, is higher when compared with rituximab and similar to that with continuous thrombopoietin-receptor agonists (TPO-RA) administration. Splenectomy should continue to be offered to patients failing initial treatments in the absence of increased surgery-related risks. The higher lifelong safety concerns with splenectomy (increased risk of infection, shared in part with rituximab, and of thrombosis, in common with TPO-RA) and a mortality <1-2%, justify postponing surgery to the chronic phase, when spontaneous remissions are rarer...
February 26, 2018: British Journal of Haematology
Yingyi Yu, Yuanyuan Shi, Xinyi Zuo, Qi Feng, Yu Hou, Wei Tang, Yi Lu, Fan Yi, Ming Hou, Yuan Yu, Jun Peng
INTRODUCTION: Progranulin (PGRN) is emerging as a critical immune mediator involved in a variety of autoimmune disorders. However, its role in immune thrombocytopenia (ITP) remains unclear. MATERIALS AND METHODS: In this study, the enzyme-linked immunosorbent assay was used for determining the plasma levels of PGRN in ITP patients vs. healthy controls. In addition, the role of PGRN in ITP was investigated in two kinds of ITP murine models. Further, we explored whether PGRN functioned by affecting the number of T regulatory cells (Tregs) using flow cytometry...
February 17, 2018: Thrombosis Research
Phoebe B Mitchell, Sonja I Ziniel, Sarah K Savage, Kurt D Christensen, Elissa R Weitzman, Robert C Green, Noelle L Huntington, Debra J Mathews, Ingrid A Holm
The opportunity to receive individual research results (IRRs) in accordance with personal preferences may incentivize biobank participation and maximize perceived benefit. This trial investigated the relationship between parents' preferences and intent to participate (ITP) in biobank research utilizing their child's genetic information. We randomized parents of pediatric patients to four hypothetical biobanks, one of which employed a preference-setting model for return of results regarding their child. ITP was highest among those desiring all types of IRRs (93...
January 1, 2018: Journal of Empirical Research on Human Research Ethics: JERHRE
Jian-Chun Guo, Yi Zheng, Hai-Tao Chen, Haixia Zhou, Xian-Hui Huang, Li-Ping Zhong, Huai-Bin Zhou, Yu Huang, Dan-Li Xie, Yong-Liang Lou
Background and Aim: Thrombopoietin receptor agonists (TPO-RAs) have been shown to be safe and effective for adults with chronic immune thrombocytopenia (ITP). The aim of this meta-analysis is to assess the efficacy and safety of thrombopoietin receptor agonists for children with chronic ITP. Materials and Methods: Clinical randomized controlled trials (RCTs) evaluating the efficacy and safety of TPO-RAs in pediatric ITP patients published up to June 2017 were retrieved from PubMed, Cochrane Library, and Embase databases...
January 23, 2018: Oncotarget
Bernardus G Goldman, Mark P Hehir, Sahr Yambasu, Edward M O'Donnell
Thrombocytopenia, defined as a platelet count less than 150,000 per microlitre, occurs in 7-12% of all pregnancies. Aside from anaemia, it is the most common haematological disorder in pregnancy. Despite its frequent occurrence, thrombocytopenia often leads to difficulties of diagnosis and management in pregnancy. Typically, a pregnant woman will have platelet counts of 150,000 to 450,000 per microlitre and platelet counts may be slightly lower than those of healthy, non-pregnant controls. Approximately 8% of pregnant women will develop mild thrombocytopenia (100,000-150,000 per microlitre) and while 65% of these women will have no underlying pathology, all pregnant women with platelet counts of less than 100,000 per microlitre should undergo further clinical and laboratory assessment...
February 21, 2018: European Journal of Haematology
Tally Rosenfeld, Moran Bercovici
We present a novel microfluidic paper-based analytical device (μPAD) which utilizes the native high electroosmotic flow (EOF) in nitrocellulose to achieve stationary isotachophoresis (ITP) focusing. This approach decouples sample accumulation from the length of the channel, resulting in significant focusing over short channel lengths. We provide a brief theory for EOF-balanced ITP focusing under continuous injection from a depleting reservoir and present the design of a short (7 mm) paper-based microfluidic channel, which allows a 200 μL sample to be processed in approximately 6 min, resulting in a 20 000-fold increase in concentration - a full order of magnitude improvement compared to previous paper-based ITP devices...
February 20, 2018: Lab on a Chip
Jia-Min Zhang, Xiao-Lu Zhu, Jing Xue, Xiao Liu, X Long Zheng, Ying-Jun Chang, Kai-Yan Liu, Xiao-Jun Huang, Xiao-Hui Zhang
Our understanding of the pathogenesis of immune thrombocytopenia (ITP) remains limited due to the complexity and heterogeneity of the disease. Recently, we observed that bone marrow mesenchymal stem cells (MSCs) derived from ITP patients exhibited growth defects and functional abnormalities that might be involved in the breakdown of self-tolerance. However, the underlying mechanism remains unclear. In this study, we profiled the expression of both mRNAs and miRNAs by utilizing the microarray technique and deciphered the mechanism underlying the impairment of MSCs derived from ITP patients (MSC-ITP)...
February 13, 2018: Functional & Integrative Genomics
Nicholas Poponea, Mohanad Suede, Mohammad Muhsin Chisti
We report a 74-year-old female who presented to the emergency department complaining of bruising and stroke-like symptoms. She underwent a negative stroke work-up but was found to have profoundly low platelets and splenomegaly on examination. An abdominal CT scan was ordered, showing pelvic lymphadenopathy. Lymphoma was suspected. However, subsequent bone marrow and lymph node biopsies showed no evidence of this. She was treated for immune thrombocytopenia purpura (ITP) to no avail while a lymphoma work-up continued...
September 2017: Case Reports in Oncology
Frank K Schubert, Nicolas Hagedorn, Taishi Yoshii, Charlotte Helfrich-Förster, Dirk Rieger
Drosophila melanogaster is a long-standing model organism in the circadian clock research. A major advantage is the relative small numbers of about 150 neurons, which built the circadian clock in Drosophila. In our recent work, we focused on the neuroanatomical properties of the lateral neurons of the clock network. By applying the multicolor-labeling technique Flybow we were able to identify the anatomical similarity of the previously described E2 subunit of the evening oscillator of the clock, which is built by the 5th small ventrolateral neuron (5th s-LNv ) and one ITP positive dorsolateral neuron (LNd )...
February 9, 2018: Journal of Comparative Neurology
Yoshiki Nakamura, Kazumasa Yokoyama, Keiko Igaki, Noboru Tsuchimori
MALT lymphoma-translocation protein 1 (Malt1) protease activity is triggered by stimulation of various immune receptors. Activation of Malt1 protease induces cleavage of negative regulators for immune responses, resulting in lymphocytes activation. Although Malt1 protease mediates the signaling process downstream of the T cell, B cell, and dectin receptors, its contribution in Fcγ receptor (FcγR) signaling has not been elucidated. In this study, we investigated the role of Malt1 protease activity in FcγR signaling using Malt1 protease-deficient (PD) mouse...
February 2, 2018: International Immunopharmacology
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