Mullite- corundum insulation material with nano crystals in matrix was fabricated by gel-casting ... more Mullite- corundum insulation material with nano crystals in matrix was fabricated by gel-casting process. The results showed that the volatilization temperature of organisms is 285°C- 600°C, there is no glass phase appeared in specimens; The mullitization begin at 1000°C, along with the raise of temperature, the quantity of mullite phase increases, especially during 1200°C- 1400°C; when the temperature is up to 1550°C, mullite becomes the main crystal phase and there are also some corundum crystals in the specimens; The specimen matrix sintered at 1550°C is consisted of nano crystals 80nm in length and 10-20nm in diameter.
With the increasing number of vehicle due to the boom of population and rapid modernisation, the ... more With the increasing number of vehicle due to the boom of population and rapid modernisation, the management of waste tire is growing problem. Reusing grinded tire rubber in concrete is a green innovation which provide an outlet for reusing waste tire. While providing certain benefits to concrete, incorporation of tire rubber results in significant loss of concrete compressive strength which hinders the potential of rubberised concrete. This paper aims to develop mathematical models on the influence of tire rubber replacement on the compressive strength of concrete using design of experiment (DoE). 33 data sets are gathered from available literature on concrete with waste tire rubber as partial replacement of fine aggregate. Response surface methodology (RSM) model of rubberised concrete compressive strength shows great accuracy with coefficient of determination (R2) of 0.9923 and root-mean-square error (RMSE) of 2.368. Regression analysis on the strength index of rubberised concrete...
Background Although clinical studies have not shown a significant difference between the risk of ... more Background Although clinical studies have not shown a significant difference between the risk of bleeding in acutely ill medical patients receiving pharmacologic venous thromboembolism (VTE) prophylaxis and those receiving placebo, fear of bleeding may lead physicians to withhold pharmacologic prophylaxis for patients who should receive it. We therefore aimed to determine the incidence of, and risk factors for in-hospital bleeding in hospitalized acutely ill medical patients in IMPROVE, an international, observational registry. Methods Patients aged ≥18 years, hospitalized ≥3 days with an acute medical illness have been enrolled consecutively since July 2002. Exclusion criteria: therapeutic antithrombotics/thrombolytics at admission, major surgery or trauma during 3 months prior to admission, and VTE treatment within 24 hours of admission. Patients bleeding immediately before, or at admission were excluded from this analysis. Factors present at admission and associated with increase...
Background Acutely ill medical patients at risk for venous thromboembolism (VTE) should receive V... more Background Acutely ill medical patients at risk for venous thromboembolism (VTE) should receive VTE prophylaxis. However, factors perceived by physicians to increase patients’ risk of bleeding may influence VTE prophylaxis practices. In this analysis from The International Medical Prevention Registry on Venous Thromboembolism (IMPROVE), we examined whether perceived risk factors for bleeding had a significant influence on physicians’ prescribing of in-hospital prophylaxis in acutely ill medical patients. Methods Patients aged ≥18 years and hospitalized ≥3 days with an acute medical illness have been enrolled consecutively since July 2002. Risk factors considered were: severe renal failure, known bleeding disorder, hemorrhagic stroke, thrombocytopenia, bacterial endocarditis, active gastroduodenal ulcer, NSAID use, hepatic failure, age, immobility and alcoholism. Factors associated with different prescription rates of prophylaxis compared with rates in patients without these factors ...
Heparin, in various forms, is used in a variety of conditions including prophylaxis and treatment... more Heparin, in various forms, is used in a variety of conditions including prophylaxis and treatment of thromboembolic disorders. Although the most common adverse effect related to the use of heparin is bleeding, heparin-induced thrombocytopenia (HIT) can also occur. Two types of HIT exist, HIT type I and type II. HIT type I is a mild and self-limiting disease in which the patient’s platelet count may decrease slightly but will recover with continued treatment. This is in contrast to HIT type II, which may lead to potentially devastating complications. Patients with HIT type II are at increased risk for thromboembolic complications that are mediated through autoimmune reactions and therefore require anticoagulation with danaparoid or one of the direct thrombin inhibitors, including lepirudin, argatroban, or bivalirudin. Limited data are available on the use of these agents in special populations including patients who are pregnant or those undergoing procedures such as percutaneous cor...
Over the last decade, there have been numerous developments and changes in treatment practices fo... more Over the last decade, there have been numerous developments and changes in treatment practices for the management of patients with immune thrombocytopenia (ITP). This article is an update of the International Consensus Report published in 2010. A critical review was performed to identify all relevant articles published between 2009 and 2018. An expert panel screened, reviewed, and graded the studies and formulated the updated consensus recommendations based on the new data. The final document provides consensus recommendations on the diagnosis and management of ITP in adults, during pregnancy, and in children, as well as quality-of-life considerations.
SummaryMegakaryocyte and platelet Fcγ receptors (FcR) are of importance in the pathophysiology of... more SummaryMegakaryocyte and platelet Fcγ receptors (FcR) are of importance in the pathophysiology of immune complex-mediated thrombocytopenias such as heparin-induced thrombocytopenia. In this study, FcγR proteins and mRNAs in normal human megakaryocytes were examined. FcγR proteins were studied with immunocytochemical staining, dual colour flow cytometry and immunoprecipitation using monoclonal antibodies against FcγR I, FcγR II and FcγR III. FcγR mRNAs were measured with biotinylated cDNA or oligonucleotide probes using a novel quantitative in situ hybridization technique. Using these techniques, FcγR II protein and mRNA, but not FcγR I and FcγR III proteins and transcripts were detected in megakaryocytes. Further, transcript analysis showed that megakaryocytes contain only the transcript of FcγR IIA gene but no transcripts of FcγR IIB nor FcγR IIC genes; FcγR IIA transcripts with and without the transmembrane (TM) exon are present in approximately equal proportions. In contrast, neu...
Thrombocytopenia is a common clinical condition and requires more effective treatments. Our previ... more Thrombocytopenia is a common clinical condition and requires more effective treatments. Our previous original work confirmed that 5-HT contributes to the expansion of cord blood stem/progenitor cells (CD34+/CD41+CD61+) and haematopoietic reconstitution in NOD/SCID mice, and through 5-HT2R and Erk1/2 pathway, 5-HT remodel F-actin organization, promoting megakaryocytes to pro-platelet formation (Stem Cells, 2007; 2014). It is suggested that there is a subtype of haematopoietic stem cells (CD34+5HT2R+) with the potential to differentiate into megakaryocytes (CD41+5HT2R+). We studied the specific functions of cells through subsequent experiments, including receptor expression and signaling pathways. Results showed that: (1) The presence of 5-HT2 receptors on CD34+ and CD41+ cells; (2) 5-HT activated the PI3K/AKT pathway and the Wnt/β-catenin pathway via 5-HT2R in CD34+ and CD41+ cells, with anti-apoptotic and pro-proliferative functions; (3) These CD34+5HT2R+ differentiated CD41+5HT2R+ ...
Background: Previous studies have shown that the vascular niche was damaged in patients with immu... more Background: Previous studies have shown that the vascular niche was damaged in patients with immune thrombocytopenia (ITP). It is mainly manifested that the migration and tube-formation ability of bone marrow endothelial progenitor cells (BM-EPCs) were significantly reduced. Endothelial cells as an important part of the vascular niche play an important role in regulation of megakaryocytes and platelet hematopoiesis. Our previous studies suggested that thrombopoietin (TPO) has a protective effect on human endothelial cells. This study aim to investigate whether TPO has a protective effect in EPCs of ITP patients and to explore its mechanism. Methods: BM-EPCs were isolated from ITP patients, and divided into two groups: TPO-treated group and TPO-free (control group). CCK8 was used to explore whether TPO has proliferative effect on BM-EPCs. BM-EPCs was identified by flow cytometry with co-expression of mouse anti-humanCD133, mouse anti-human CD34 and mouse anti-human vascular endotheli...
Adverse drug effects are common in clinical practice and often have a negative impact on patient ... more Adverse drug effects are common in clinical practice and often have a negative impact on patient safety. Heparin and heparin-derived drugs may induce an immune reaction, termed heparin-induced thrombocytopenia (HIT). HIT is mediated by IgG antibodies with specificity for heparin/platelet factor 4 (PF4) antigenic complexes. HIT is a hypercoagulable state which often causes severe and extensive thrombosis that results in high morbidity and mortality. The prevailing view is that these immune complexes activate platelets via FcγRIIa receptors leading to thrombocytopenia and thrombosis. Neutrophil extracellular traps (NETs) are DNA-containing structures released by neutrophils that are increasingly being reported in patients with infection and thrombosis associated with various autoimmune and non-immune disorders. Here we show that HIT immune complexes directly activate neutrophils via FcγRIIa and induce NETs formation. In addition, NETosis is also induced by activated platelets/neutroph...
Thrombopoietin (TPO), the specific cytokine that regulates platelet production, is expressed in h... more Thrombopoietin (TPO), the specific cytokine that regulates platelet production, is expressed in human bone marrow (BM), kidney, and liver. There appears to be no regulation of TPO in the kidney and liver, but TPO messenger RNA (mRNA) expression can be modulated in the stromal cells of the BM. In this study, we used primary human BM stromal cells as a model to study the regulation of TPO mRNA expression in response to various platelet -granular proteins. We showed that platelet-derived growth factor (PDGF) BB and fibroblast growth factor (FGF) 2 stimulated TPO mRNA expression in both a dose-dependent and time-dependent manner. The addition of 50 ng/mL of PDGF and 20 ng/mL of FGF resulted in maximal induction of TPO mRNA expression in 4 hours. We also found that platelet factor 4 (PF4), thrombospondin (TSP), and transforming growth factor-beta (TGF-β) are negative modulators of megakaryocytopoiesis. We observed suppression in TPO mRNA expression with 1 μg/mL of both PF4 and TSP and 5...
3702 Introduction: Romiplostim is a novel peptibody that increases platelet counts by a mechanism... more 3702 Introduction: Romiplostim is a novel peptibody that increases platelet counts by a mechanism similar to endogenous thrombopoietin, and is approved for the treatment of chronic ITP. ITP is characterized by low platelet counts due to increased platelet destruction and suboptimal platelet production. The response rate to ITP therapies is variable and may be associated with substantial adverse effects. Splenectomy is commonly used as a treatment for ITP because it removes the major site of platelet destruction. A recent consensus report (Provan et al., 2010, 168–86) recommends delaying splenectomy for 6–12 months, in keeping with the new definition for chronic ITP (Rodeghiero et al., Blood 2009, 2386–93); therefore, we evaluated patients who had been diagnosed with ITP ≤1 year who participated in a recent study of romiplostim versus standard of care (SOC). Methods: A randomized, open-label study was conducted in nonsplenectomized adult patients with ITP. The co-primary study endpoi...
Objective: The infusion of bone marrow cells into the damaged brain has been proposed as a new cl... more Objective: The infusion of bone marrow cells into the damaged brain has been proposed as a new clinical practice for this disorder. Alternatively, hematopoietic growth factors may have a direct role on neural protection or have a mobilizing effect on bone marrow stem/progenitor cells to circulation for brain repair. Based on our previous findings, there are many similarities between megakaryocytes and neurons on functions and antigen expression such as neural marker MAP2, GFAP and Tau, 5-HT2A, 2B and 2C receptors (Stem Cells, 2014). Thrombopoietin (TPO) is a growth factor for megakaryocytic lineage. We postulate that TPO may play a role on neural protection or regeneration. The effect of TPO on nervous system has not been well investigated. Methods: To validate this hypothesis, we investigated the expression and role of TPO/TPO receptors in neural cells and a neonatal rat model of hypoxic-ischemic (HIE) brain damage. Results: To investigate the effect of TPO on in-vivo neural protec...
Background Patients with previous or current cancer have an increased risk for venous thromboembo... more Background Patients with previous or current cancer have an increased risk for venous thromboembolism (VTE). However, little data is available on physician’s practices for providing VTE prophylaxis to these patients. The aim of this analysis of the International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) was to characterize VTE prophylaxis practices in acutely ill hospitalized medical patients who had previous cancer or currently active cancer. Methods Patient recruitment began in July 2002. Patients ≥18 years old and hospitalized for ≥3 days with an acute medical illness are enrolled consecutively. Exclusion criteria are: therapeutic antithrombotic agents or thrombolytics at admission, major surgery or trauma during 3 months prior to admission, and VTE treatment within 24 hours of admission. Results Data were from 4315 patients enrolled up to 30 June 2004 in 37 hospitals in 11 countries. 578 (13%) patients had currently active cancer (6% as the primary admissio...
Melanoma incidence is increasing worldwide, and although drugs such as BRAF/MEK small-molecule in... more Melanoma incidence is increasing worldwide, and although drugs such as BRAF/MEK small-molecule inhibitors and immune checkpoint antibodies improve patient outcomes, most patients ultimately fail these therapies and alternative treatment strategies are urgently needed. DNAzymes have recently undergone clinical trials with signs of efficacy and no serious adverse events attributable to the DNAzyme. Here we investigated c-Jun expression in human primary and metastatic melanoma. We also explored the role of T cell immunity in DNAzyme inhibition of primary melanoma growth and the prevention of growth in non-treated tumors after the cessation of treatment in a mouse model. c-Jun was expressed in 80% of melanoma cells in human primary melanomas (n = 17) and in 83% of metastatic melanoma cells (n = 38). In contrast, c-Jun was expressed in only 11% of melanocytes in benign nevi (n = 24). Dz13, a DNAzyme targeting c-Jun/AP-1, suppressed both Dz13-injected and untreated B16F10 melanoma growth ...
Journal of visualized experiments : JoVE, Dec 27, 2017
Platelet production occurs principally in the bone marrow in a process known as thrombopoiesis. D... more Platelet production occurs principally in the bone marrow in a process known as thrombopoiesis. During thrombopoiesis, hematopoietic progenitor cells differentiate to form platelet precursors called megakaryocytes, which terminally differentiate to release platelets from long cytoplasmic processes termed proplatelets. Megakaryocytes are rare cells confined to the bone marrow and are therefore difficult to harvest in sufficient numbers for laboratory use. Efficient production of human megakaryocytes can be achieved in vitro by culturing CD34cells under suitable conditions. The protocol detailed here describes isolation of CD34cells by magnetic cell sorting from umbilical cord blood samples. The necessary steps to produce highly pure, mature megakaryocytes under serum-free conditions are described. Details of phenotypic analysis of megakaryocyte differentiation and determination of proplatelet formation and platelet production are also provided. Effectors that influence megakaryocyte ...
Primary immune thrombocytopenia is an autoimmune disorder characterized by increased platelet des... more Primary immune thrombocytopenia is an autoimmune disorder characterized by increased platelet destruction and insufficient platelet production without another identified underlying disorder. Splenectomy may alter responsiveness to treatment and/or increase the risk of thrombosis, infection, and pulmonary hypertension. This analysis evaluated the safety and efficacy of the thrombopoietin receptor agonist romiplostim in splenectomized and nonsplenectomized adults with primary immune thrombocytopenia. Data were pooled across 13 completed clinical studies in adults with immune thrombocytopenia from 2002-2014. Adverse event rates were adjusted for time of exposure. Results were considered different when 95% confidence intervals were nonoverlapping. Safety was analyzed for 1111 patients (395 splenectomized; 716 nonsplenectomized) who received romiplostim or control (placebo or standard of care). At baseline, splenectomized patients had a longer median duration of immune thrombocytopenia a...
Mullite- corundum insulation material with nano crystals in matrix was fabricated by gel-casting ... more Mullite- corundum insulation material with nano crystals in matrix was fabricated by gel-casting process. The results showed that the volatilization temperature of organisms is 285°C- 600°C, there is no glass phase appeared in specimens; The mullitization begin at 1000°C, along with the raise of temperature, the quantity of mullite phase increases, especially during 1200°C- 1400°C; when the temperature is up to 1550°C, mullite becomes the main crystal phase and there are also some corundum crystals in the specimens; The specimen matrix sintered at 1550°C is consisted of nano crystals 80nm in length and 10-20nm in diameter.
With the increasing number of vehicle due to the boom of population and rapid modernisation, the ... more With the increasing number of vehicle due to the boom of population and rapid modernisation, the management of waste tire is growing problem. Reusing grinded tire rubber in concrete is a green innovation which provide an outlet for reusing waste tire. While providing certain benefits to concrete, incorporation of tire rubber results in significant loss of concrete compressive strength which hinders the potential of rubberised concrete. This paper aims to develop mathematical models on the influence of tire rubber replacement on the compressive strength of concrete using design of experiment (DoE). 33 data sets are gathered from available literature on concrete with waste tire rubber as partial replacement of fine aggregate. Response surface methodology (RSM) model of rubberised concrete compressive strength shows great accuracy with coefficient of determination (R2) of 0.9923 and root-mean-square error (RMSE) of 2.368. Regression analysis on the strength index of rubberised concrete...
Background Although clinical studies have not shown a significant difference between the risk of ... more Background Although clinical studies have not shown a significant difference between the risk of bleeding in acutely ill medical patients receiving pharmacologic venous thromboembolism (VTE) prophylaxis and those receiving placebo, fear of bleeding may lead physicians to withhold pharmacologic prophylaxis for patients who should receive it. We therefore aimed to determine the incidence of, and risk factors for in-hospital bleeding in hospitalized acutely ill medical patients in IMPROVE, an international, observational registry. Methods Patients aged ≥18 years, hospitalized ≥3 days with an acute medical illness have been enrolled consecutively since July 2002. Exclusion criteria: therapeutic antithrombotics/thrombolytics at admission, major surgery or trauma during 3 months prior to admission, and VTE treatment within 24 hours of admission. Patients bleeding immediately before, or at admission were excluded from this analysis. Factors present at admission and associated with increase...
Background Acutely ill medical patients at risk for venous thromboembolism (VTE) should receive V... more Background Acutely ill medical patients at risk for venous thromboembolism (VTE) should receive VTE prophylaxis. However, factors perceived by physicians to increase patients’ risk of bleeding may influence VTE prophylaxis practices. In this analysis from The International Medical Prevention Registry on Venous Thromboembolism (IMPROVE), we examined whether perceived risk factors for bleeding had a significant influence on physicians’ prescribing of in-hospital prophylaxis in acutely ill medical patients. Methods Patients aged ≥18 years and hospitalized ≥3 days with an acute medical illness have been enrolled consecutively since July 2002. Risk factors considered were: severe renal failure, known bleeding disorder, hemorrhagic stroke, thrombocytopenia, bacterial endocarditis, active gastroduodenal ulcer, NSAID use, hepatic failure, age, immobility and alcoholism. Factors associated with different prescription rates of prophylaxis compared with rates in patients without these factors ...
Heparin, in various forms, is used in a variety of conditions including prophylaxis and treatment... more Heparin, in various forms, is used in a variety of conditions including prophylaxis and treatment of thromboembolic disorders. Although the most common adverse effect related to the use of heparin is bleeding, heparin-induced thrombocytopenia (HIT) can also occur. Two types of HIT exist, HIT type I and type II. HIT type I is a mild and self-limiting disease in which the patient’s platelet count may decrease slightly but will recover with continued treatment. This is in contrast to HIT type II, which may lead to potentially devastating complications. Patients with HIT type II are at increased risk for thromboembolic complications that are mediated through autoimmune reactions and therefore require anticoagulation with danaparoid or one of the direct thrombin inhibitors, including lepirudin, argatroban, or bivalirudin. Limited data are available on the use of these agents in special populations including patients who are pregnant or those undergoing procedures such as percutaneous cor...
Over the last decade, there have been numerous developments and changes in treatment practices fo... more Over the last decade, there have been numerous developments and changes in treatment practices for the management of patients with immune thrombocytopenia (ITP). This article is an update of the International Consensus Report published in 2010. A critical review was performed to identify all relevant articles published between 2009 and 2018. An expert panel screened, reviewed, and graded the studies and formulated the updated consensus recommendations based on the new data. The final document provides consensus recommendations on the diagnosis and management of ITP in adults, during pregnancy, and in children, as well as quality-of-life considerations.
SummaryMegakaryocyte and platelet Fcγ receptors (FcR) are of importance in the pathophysiology of... more SummaryMegakaryocyte and platelet Fcγ receptors (FcR) are of importance in the pathophysiology of immune complex-mediated thrombocytopenias such as heparin-induced thrombocytopenia. In this study, FcγR proteins and mRNAs in normal human megakaryocytes were examined. FcγR proteins were studied with immunocytochemical staining, dual colour flow cytometry and immunoprecipitation using monoclonal antibodies against FcγR I, FcγR II and FcγR III. FcγR mRNAs were measured with biotinylated cDNA or oligonucleotide probes using a novel quantitative in situ hybridization technique. Using these techniques, FcγR II protein and mRNA, but not FcγR I and FcγR III proteins and transcripts were detected in megakaryocytes. Further, transcript analysis showed that megakaryocytes contain only the transcript of FcγR IIA gene but no transcripts of FcγR IIB nor FcγR IIC genes; FcγR IIA transcripts with and without the transmembrane (TM) exon are present in approximately equal proportions. In contrast, neu...
Thrombocytopenia is a common clinical condition and requires more effective treatments. Our previ... more Thrombocytopenia is a common clinical condition and requires more effective treatments. Our previous original work confirmed that 5-HT contributes to the expansion of cord blood stem/progenitor cells (CD34+/CD41+CD61+) and haematopoietic reconstitution in NOD/SCID mice, and through 5-HT2R and Erk1/2 pathway, 5-HT remodel F-actin organization, promoting megakaryocytes to pro-platelet formation (Stem Cells, 2007; 2014). It is suggested that there is a subtype of haematopoietic stem cells (CD34+5HT2R+) with the potential to differentiate into megakaryocytes (CD41+5HT2R+). We studied the specific functions of cells through subsequent experiments, including receptor expression and signaling pathways. Results showed that: (1) The presence of 5-HT2 receptors on CD34+ and CD41+ cells; (2) 5-HT activated the PI3K/AKT pathway and the Wnt/β-catenin pathway via 5-HT2R in CD34+ and CD41+ cells, with anti-apoptotic and pro-proliferative functions; (3) These CD34+5HT2R+ differentiated CD41+5HT2R+ ...
Background: Previous studies have shown that the vascular niche was damaged in patients with immu... more Background: Previous studies have shown that the vascular niche was damaged in patients with immune thrombocytopenia (ITP). It is mainly manifested that the migration and tube-formation ability of bone marrow endothelial progenitor cells (BM-EPCs) were significantly reduced. Endothelial cells as an important part of the vascular niche play an important role in regulation of megakaryocytes and platelet hematopoiesis. Our previous studies suggested that thrombopoietin (TPO) has a protective effect on human endothelial cells. This study aim to investigate whether TPO has a protective effect in EPCs of ITP patients and to explore its mechanism. Methods: BM-EPCs were isolated from ITP patients, and divided into two groups: TPO-treated group and TPO-free (control group). CCK8 was used to explore whether TPO has proliferative effect on BM-EPCs. BM-EPCs was identified by flow cytometry with co-expression of mouse anti-humanCD133, mouse anti-human CD34 and mouse anti-human vascular endotheli...
Adverse drug effects are common in clinical practice and often have a negative impact on patient ... more Adverse drug effects are common in clinical practice and often have a negative impact on patient safety. Heparin and heparin-derived drugs may induce an immune reaction, termed heparin-induced thrombocytopenia (HIT). HIT is mediated by IgG antibodies with specificity for heparin/platelet factor 4 (PF4) antigenic complexes. HIT is a hypercoagulable state which often causes severe and extensive thrombosis that results in high morbidity and mortality. The prevailing view is that these immune complexes activate platelets via FcγRIIa receptors leading to thrombocytopenia and thrombosis. Neutrophil extracellular traps (NETs) are DNA-containing structures released by neutrophils that are increasingly being reported in patients with infection and thrombosis associated with various autoimmune and non-immune disorders. Here we show that HIT immune complexes directly activate neutrophils via FcγRIIa and induce NETs formation. In addition, NETosis is also induced by activated platelets/neutroph...
Thrombopoietin (TPO), the specific cytokine that regulates platelet production, is expressed in h... more Thrombopoietin (TPO), the specific cytokine that regulates platelet production, is expressed in human bone marrow (BM), kidney, and liver. There appears to be no regulation of TPO in the kidney and liver, but TPO messenger RNA (mRNA) expression can be modulated in the stromal cells of the BM. In this study, we used primary human BM stromal cells as a model to study the regulation of TPO mRNA expression in response to various platelet -granular proteins. We showed that platelet-derived growth factor (PDGF) BB and fibroblast growth factor (FGF) 2 stimulated TPO mRNA expression in both a dose-dependent and time-dependent manner. The addition of 50 ng/mL of PDGF and 20 ng/mL of FGF resulted in maximal induction of TPO mRNA expression in 4 hours. We also found that platelet factor 4 (PF4), thrombospondin (TSP), and transforming growth factor-beta (TGF-β) are negative modulators of megakaryocytopoiesis. We observed suppression in TPO mRNA expression with 1 μg/mL of both PF4 and TSP and 5...
3702 Introduction: Romiplostim is a novel peptibody that increases platelet counts by a mechanism... more 3702 Introduction: Romiplostim is a novel peptibody that increases platelet counts by a mechanism similar to endogenous thrombopoietin, and is approved for the treatment of chronic ITP. ITP is characterized by low platelet counts due to increased platelet destruction and suboptimal platelet production. The response rate to ITP therapies is variable and may be associated with substantial adverse effects. Splenectomy is commonly used as a treatment for ITP because it removes the major site of platelet destruction. A recent consensus report (Provan et al., 2010, 168–86) recommends delaying splenectomy for 6–12 months, in keeping with the new definition for chronic ITP (Rodeghiero et al., Blood 2009, 2386–93); therefore, we evaluated patients who had been diagnosed with ITP ≤1 year who participated in a recent study of romiplostim versus standard of care (SOC). Methods: A randomized, open-label study was conducted in nonsplenectomized adult patients with ITP. The co-primary study endpoi...
Objective: The infusion of bone marrow cells into the damaged brain has been proposed as a new cl... more Objective: The infusion of bone marrow cells into the damaged brain has been proposed as a new clinical practice for this disorder. Alternatively, hematopoietic growth factors may have a direct role on neural protection or have a mobilizing effect on bone marrow stem/progenitor cells to circulation for brain repair. Based on our previous findings, there are many similarities between megakaryocytes and neurons on functions and antigen expression such as neural marker MAP2, GFAP and Tau, 5-HT2A, 2B and 2C receptors (Stem Cells, 2014). Thrombopoietin (TPO) is a growth factor for megakaryocytic lineage. We postulate that TPO may play a role on neural protection or regeneration. The effect of TPO on nervous system has not been well investigated. Methods: To validate this hypothesis, we investigated the expression and role of TPO/TPO receptors in neural cells and a neonatal rat model of hypoxic-ischemic (HIE) brain damage. Results: To investigate the effect of TPO on in-vivo neural protec...
Background Patients with previous or current cancer have an increased risk for venous thromboembo... more Background Patients with previous or current cancer have an increased risk for venous thromboembolism (VTE). However, little data is available on physician’s practices for providing VTE prophylaxis to these patients. The aim of this analysis of the International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) was to characterize VTE prophylaxis practices in acutely ill hospitalized medical patients who had previous cancer or currently active cancer. Methods Patient recruitment began in July 2002. Patients ≥18 years old and hospitalized for ≥3 days with an acute medical illness are enrolled consecutively. Exclusion criteria are: therapeutic antithrombotic agents or thrombolytics at admission, major surgery or trauma during 3 months prior to admission, and VTE treatment within 24 hours of admission. Results Data were from 4315 patients enrolled up to 30 June 2004 in 37 hospitals in 11 countries. 578 (13%) patients had currently active cancer (6% as the primary admissio...
Melanoma incidence is increasing worldwide, and although drugs such as BRAF/MEK small-molecule in... more Melanoma incidence is increasing worldwide, and although drugs such as BRAF/MEK small-molecule inhibitors and immune checkpoint antibodies improve patient outcomes, most patients ultimately fail these therapies and alternative treatment strategies are urgently needed. DNAzymes have recently undergone clinical trials with signs of efficacy and no serious adverse events attributable to the DNAzyme. Here we investigated c-Jun expression in human primary and metastatic melanoma. We also explored the role of T cell immunity in DNAzyme inhibition of primary melanoma growth and the prevention of growth in non-treated tumors after the cessation of treatment in a mouse model. c-Jun was expressed in 80% of melanoma cells in human primary melanomas (n = 17) and in 83% of metastatic melanoma cells (n = 38). In contrast, c-Jun was expressed in only 11% of melanocytes in benign nevi (n = 24). Dz13, a DNAzyme targeting c-Jun/AP-1, suppressed both Dz13-injected and untreated B16F10 melanoma growth ...
Journal of visualized experiments : JoVE, Dec 27, 2017
Platelet production occurs principally in the bone marrow in a process known as thrombopoiesis. D... more Platelet production occurs principally in the bone marrow in a process known as thrombopoiesis. During thrombopoiesis, hematopoietic progenitor cells differentiate to form platelet precursors called megakaryocytes, which terminally differentiate to release platelets from long cytoplasmic processes termed proplatelets. Megakaryocytes are rare cells confined to the bone marrow and are therefore difficult to harvest in sufficient numbers for laboratory use. Efficient production of human megakaryocytes can be achieved in vitro by culturing CD34cells under suitable conditions. The protocol detailed here describes isolation of CD34cells by magnetic cell sorting from umbilical cord blood samples. The necessary steps to produce highly pure, mature megakaryocytes under serum-free conditions are described. Details of phenotypic analysis of megakaryocyte differentiation and determination of proplatelet formation and platelet production are also provided. Effectors that influence megakaryocyte ...
Primary immune thrombocytopenia is an autoimmune disorder characterized by increased platelet des... more Primary immune thrombocytopenia is an autoimmune disorder characterized by increased platelet destruction and insufficient platelet production without another identified underlying disorder. Splenectomy may alter responsiveness to treatment and/or increase the risk of thrombosis, infection, and pulmonary hypertension. This analysis evaluated the safety and efficacy of the thrombopoietin receptor agonist romiplostim in splenectomized and nonsplenectomized adults with primary immune thrombocytopenia. Data were pooled across 13 completed clinical studies in adults with immune thrombocytopenia from 2002-2014. Adverse event rates were adjusted for time of exposure. Results were considered different when 95% confidence intervals were nonoverlapping. Safety was analyzed for 1111 patients (395 splenectomized; 716 nonsplenectomized) who received romiplostim or control (placebo or standard of care). At baseline, splenectomized patients had a longer median duration of immune thrombocytopenia a...
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