Preoperative intra-aortic balloon pump in patients with ST-elevation myocardial infarction undergoing urgent cardiac bypass surgery.

Background: In patients with ST-elevation myocardial infarction (STEMI), either with or without cardiogenic shock, mechanical circulatory support with an intra-aortic balloon pump (IABP) is not associated with lower mortality. However, in STEMI patients undergoing urgent coronary artery bypass grafting (CABG), preoperative insertion of an IABP has been suggested to reduce mortality. In this study, the effect of preoperative IABP use on mortality in STEMI patients undergoing urgent CABG was investigated.

Anatomical position of the mandibular condyle after open versus closed treatment of unilateral fractures: A three-dimensional analysis.

This study aimed to compare open and closed treatment for unilateral mandibular condyle neck and base fractures by final three-dimensional (3D) condylar position at 6 months follow-up. 3D position was associated with mandibular functioning and pain. A total of 21 patients received open (n = 11) or closed (n = 10) treatment.

Reliability of 3D Stereophotogrammetry for Measuring Postoperative Facial Swelling.

This study aimed to determine the reliability of three-dimensional (3D) stereophotogrammetry as a measurement instrument for evaluating soft tissue changes in the head and neck area. Twelve patients received a bilateral sagittal split osteotomy (BSSO). Test and retest 3D photographs were captured within the first three postoperative weeks, and a reference 3D photograph was capture at three months postoperatively.

Standard MRI May Not Predict Specific Acute Anterior Cruciate Ligament Rupture Characteristics.

Background: There has been renewed interest in the concept of anterior cruciate ligament (ACL) suture repair (ACLSR). Morphologic characteristics of the ruptured ACL remnant play a role in deciding whether a patient is eligible for ACLSR. However, no classification of these characteristics of ACL rupture on magnetic resonance imaging (MRI) scans has yet been compared with intraoperative findings in the context of ACLSR.

Autophagy inhibition as a potential future targeted therapy for ETV6-RUNX1-driven B-cell precursor acute lymphoblastic leukemia.

Translocation t(12;21), resulting in the ETV6-RUNX1 (or TEL-AML1) fusion protein, is present in 25% of pediatric patients with B-cell precursor acute lymphoblastic leukemia and is considered a first hit in leukemogenesis. A targeted therapy approach is not available for children with this subtype of leukemia. To identify the molecular mechanisms underlying ETV6-RUNX1-driven leukemia, we performed gene expression profiling of healthy hematopoietic progenitors in which we ectopically expressed ETV6-RUNX1.

Short-Term Results of a Rehabilitation Program for Service Members With Lower Leg Pain and the Evaluation of Patient Characteristics.

Introduction: Lower leg pain (LLP), including medial tibial stress syndrome (MTSS) and chronic exertional compartment syndrome (CECS), remains a major problem for the military.

Objective: Evaluation of patient characteristics and short-term results of the rehabilitation program for service members used in the Military Rehabilitation Centre Aardenburg.

Methods: This retrospective study includes 161 service members of the Netherlands Armed Forces.

Cell signalling during human eosinophil differentiation.

Eosinophil differentiation is a complex series of events regulated by cytokines at multiple levels, including proliferation, survival, and maturation. The development of an ex vivo eosinophil differentiation model, using the current knowledge on factors involved in this process, has facilitated efforts to understand the molecular mechanisms underlying human eosinophil development. Differentiation of human hematopoietic progenitor cells, isolated by density centrifugation and immunomagnetic cell separation, towards mature eosinophils, involves a 17-day culture period in the presence of a mixture of cytokines.

Determination of the optimal length of insertion of central venous catheters in pediatric patients by endovascular ECG.

Background: In children the position of the tip of central venous catheters (CVC) is most often examined by chest radiography. Endovascular electrocardiography (ECG), using the CVC as an electrode, permits the correct placement of a CVC without the need for a chest X-ray. The use of a commercialised endovascular ECG-system (Alphacard®) for CVC-placement was evaluated in pediatric patients.

PI3K-PKB hyperactivation augments human plasmacytoid dendritic cell development and function.

Plasmacytoid dendritic cells (pDCs) are considered potential tools or targets for immunotherapy. However, current knowledge concerning methodologies to manipulate their development or function remains limited. Here, we investigated the role of the phosphatidylinositol 3-kinase (PI3K)-protein kinase B (PKB)-mammalian target of rapamycin (mTOR) axis in human pDC development, survival, and function.

Molecular mechanisms underlying adhesion and migration of hematopoietic stem cells.

Hematopoietic stem cell transplantation is the most powerful treatment modality for a large number of hematopoietic malignancies, including leukemia. Successful hematopoietic recovery after transplantation depends on homing of hematopoietic stem cells to the bone marrow and subsequent lodging of those cells in specific niches in the bone marrow. Migration of hematopoietic stem cells to the bone marrow is a highly regulated process that requires correct regulation of the expression and activity of various molecules including chemoattractants, selectins and integrins.

The PI3K/PKB signaling module as key regulator of hematopoiesis: implications for therapeutic strategies in leukemia.

An important mediator of cytokine signaling implicated in regulation of hematopoiesis is the PI3K/protein kinase B (PKB/c-Akt) signaling module. Constitutive activation of this signaling module has been observed in a large group of leukemias. Because activation of this signaling pathway has been demonstrated to be sufficient to induce hematologic malignancies and is thought to correlate with poor prognosis and enhanced drug resistance, it is considered to be a promising target for therapy.

Survival, but not maturation, is affected in neutrophil progenitors from GSD-1b patients.

Glycogen storage disease type 1b (GSD 1b) is caused by mutations in the Glucose-6-phosphate transporter and is characterized by impaired glucose homeostasis. In addition, GSD-1b is associated with chronic neutropenia resulting in recurrent infections and inflammatory bowel disease. It is unclear whether the neutropenia is solely due to enhanced apoptosis of mature neutrophils or whether aberrant neutrophil development may also contribute.

The role of PI3K/protein kinase B (PKB/c-akt) in migration and homing of hematopoietic stem and progenitor cells.

Purpose Of Review: Hematopoietic stem cell (HSC) transplantation is the most powerful treatment modality for a variety of hematological disorders. Successful hematopoietic recovery after transplantation depends on optimal homing of HSCs to the bone marrow and subsequent lodging in the HSC niche. The molecular mechanisms underlying bone marrow homing are, thus far, incompletely understood.

Eosinophil differentiation in the bone marrow is inhibited by T cell-derived IFN-gamma.

To explore whether and how T cells can affect myelopoiesis, we investigated myeloid differentiation in a model for T cell-mediated immune activation. We found that CD70-transgenic (CD70TG) mice, which have elevated numbers of interferon-γ (IFN-γ)-producing effector T cells in the periphery and bone marrow, are almost devoid of eosinophilic granulocytes. Induction of allergic airway inflammation in these mice failed to induce eosinophilia as well as airway hyperresponsiveness.

Protein kinase B (PKB/c-akt) regulates homing of hematopoietic progenitors through modulation of their adhesive and migratory properties.

Limited number of hematopoietic stem cells in umbilical cord blood (UCB) presents a problem when using UCB for stem cell transplantation. Improving their homing capacity could reduce the need for high initial cell numbers during transplantation procedures. Although it is evident that protein kinase B (PKB/c-Akt) plays an important role in regulation of migration of various cell types, a role for PKB in regulation of migration and homing of human hematopoietic stem and progenitor cells remains to be determined.

Histone deacetylase inhibition modulates cell fate decisions during myeloid differentiation.

Background: The clinical use of chromatin-modulating drugs, such as histone deacetylase inhibitors, for the treatment of bone marrow failure and hematopoietic malignancies has increased dramatically over the last few years. Nonetheless, little is currently known concerning their effects on myelopoiesis.

Design And Methods: We utilized an ex vivo differentiation system in which umbilical cord blood-derived CD34(+) cells were treated with trichostatin A, sodium butyrate and valproic acid to evaluate the effect of histone deacetylase inhibitor treatment on myeloid lineage development, colony-forming potential, proliferation, and terminal neutrophil differentiation.

Tight control of MEK-ERK activation is essential in regulating proliferation, survival, and cytokine production of CD34+-derived neutrophil progenitors.

A plethora of extracellular stimuli regulate growth, survival, and differentiation responses through activation of the MEK-ERK MAPK signaling module. Using CD34+ hematopoietic progenitor cells, we describe a novel role for the MEK-ERK signaling module in the regulation of proliferation, survival, and cytokine production during neutrophil differentiation. Addition of the specific MEK1/2 inhibitor U0126 resulted in decreased proliferation of neutrophil progenitors.

Ectopic expression of C/EBPalpha and ID1 is sufficient to restore defective neutrophil development in low-risk myelodysplasia.

Background: In patients with myelodysplasia, a general defect in the multipotent stem-cell compartment results in disturbed proliferation and differentiation of the erythroid, megakaryocytic and myeloid lineages. Although a number of genetic defects in myelodysplastic progenitor cells have been described, the intracellular signaling pathways underlying aberrant regulation of myelopoiesis remain relatively undefined.

Design And Methods: Here, an ex vivo differentiation system was used to selectively screen for molecules improving defective hematopoiesis in myelodysplastic CD34(+) progenitor cells.

p38 MAP kinase inhibits neutrophil development through phosphorylation of C/EBPalpha on serine 21.

Many extracellular stimuli regulate growth, survival, and differentiation responses through activation of the dual specificity mitogen activated protein kinase (MAPK) kinase three (MKK3) and its downstream effector p38 MAPK. Using CD34+ hematopoietic progenitor cells, here we describe a novel role for MKK3-p38MAPK in the regulation of myelopoiesis. Inhibition of p38MAPK utilizing the pharmacological inhibitor SB203580, enhanced neutrophil development ex vivo, but conversely reduced eosinophil differentiation.

Mammalian target of rapamycin activity is required for expansion of CD34+ hematopoietic progenitor cells.

Background: The mammalian target of rapamycin is a conserved protein kinase known to regulate protein synthesis, cell size and proliferation. Aberrant regulation of mammalian target of rapamycin activity has been observed in hematopoietic malignancies, including acute leukemias and myelodysplastic syndromes, suggesting that correct regulation of mammalian target of rapamycin is critical for normal hematopoiesis.

Design And Methods: An ex vivo granulocyte differentiation system was utilized to investigate the role of mammalian target of rapamycin in the regulation of myelopoiesis.

Homeostatic intracellular-free Ca2+ is permissive for Rap1-mediated constitutive activation of alpha4 integrins on eosinophils.

Although much progress has been made in understanding the molecular mechanisms underlying agonist-induced "inside-out" activation of integrins, little is known about how basal levels of integrin function are maintained. This is particularly important for nonactivated eosinophils, where intermediate activation of alpha(4)beta(1) integrin supports recruitment to endothelial cells under flow conditions. Depletion of intracellular Ca(2+) and pharmacological inhibition of phospholipase C (but not other intracellular signaling molecules, including PI3K, ERK1/2, p38 MAPK, and tyrosine kinase activity) abrogated basal alpha(4) integrin activity in nonactivated eosinophils.

Protein kinase B (c-akt) regulates hematopoietic lineage choice decisions during myelopoiesis.

Hematopoiesis is a highly regulated process resulting in the formation of all blood lineages. Aberrant regulation of phosphatidylinositol-3-kinase (PI3K) signaling has been observed in hematopoietic malignancies, suggesting that regulated PI3K signaling is critical for regulation of blood cell production. An ex vivo differentiation system was used to investigate the role of PI3K and its downstream effector, protein kinase B (PKB/c-akt) in myelopoiesis.

Ligation of CD200R by CD200 is not required for normal murine myelopoiesis.

CD200R is an inhibitory receptor involved in the regulation of myeloid cells. It recruits Dok-1 and Dok-2, which are potent inhibitors of the Ras signalling pathway used by colony-stimulating factor (CSF) receptors. Dok-1/Dok-2 double knockout (DKO) mice develop leukaemia at 10-12 months of age.