Characterization of acute myeloid leukemia based on levels of global hydroxymethylation.

Patients with acute myeloid leukemia (AML) frequently harbor mutations in genes involved in the DNA (hydroxy)methylation pathway (DNMT3A, TET2, IDH1, and IDH2). In this study, we measured 5-hydroxymethylcytosine (5hmC) levels in 206 clinically and molecularly well-characterized younger adult AML patients (≤60 years) included in the European Organization for Research and Treatment of Cancer/Gruppo Italiano Malattie Ematologiche dell'Adulto (EORTC/GIMEMA) AML-12 06991 clinical trial and correlated the 5hmC levels with mutational status and overall survival (OS). In healthy control cells, 5hmC levels were confined to a narrow range (1.

The tetraspanin CD37 orchestrates the α(4)β(1) integrin-Akt signaling axis and supports long-lived plasma cell survival.

Signaling by the serine and threonine kinase Akt (also known as protein kinase B), a pathway that is common to all eukaryotic cells, is central to cell survival, proliferation, and gene induction. We sought to elucidate the mechanisms underlying regulation of the kinase activity of Akt in the immune system. We found that the four-transmembrane protein CD37 was essential for B cell survival and long-lived protective immunity.

Results of three analytical approaches on long-term efficacy of etanercept for psoriasis in daily practice.

Background: A problem encountered when analyzing long-term efficacy is that the number of patients in follow-up decreases with time for different reasons. The method used to account for missing observations for the therapy under analysis has a great influence on the inference of efficacy.

Objective: To describe the long-term efficacy of etanercept for psoriasis in daily practice using 3 analytical approaches.

High GATA2 expression is a poor prognostic marker in pediatric acute myeloid leukemia.

In acute myeloid leukemia (AML), aberrant expression and mutations of transcription factors have been correlated with disease outcome. In the present study, we performed expression and mutation screening of GATA2, which is an essential transcription factor for regulation of myeloid lineage determination, in de novo pediatric AML patients. GATA2 mutations were detected in 5 of 230 patients, representing a frequency of 2.

The lymphoid chemokine CCL21 triggers LFA-1 adhesive properties on human dendritic cells.

Dendritic cells (DCs) are the most potent APCs, involved in the induction of immunity and tolerance. Recently we showed that during differentiation of human DCs from monocyte precursors, Lymphocyte function-associated antigen-1 (LFA-1)-binding capacity is lost, although integrin expression levels were maintained constant, suggesting a different regulation mechanism of this integrin on different cell types. However, the exact role of LFA-1 in DC adhesion and migration remains obscure.

Clinical characteristics of cutaneous melanoma and second primary malignancies in a dutch hospital-based cohort of cutaneous melanoma patients.

The increasing number of living cutaneous melanoma patients and the increased risk of developing a second primary tumour incited us to analyse the clinical characteristics of cutaneous melanoma and define the frequency, site, and type of second primary cancers in cutaneous melanoma patients. We collected data on patients who visited the Department of Dermatology at the Radboud University Nijmegen Medical Centre and were newly diagnosed with cutaneous melanoma or metastasis of melanoma with unknown primary localization between 2002 and 2006. A total of 194 cases were included; eleven patients developed a subsequent melanoma, 24 had at least one basal cell carcinoma, three had at least one squamous cell carcinoma, and 21 patients had a second non-cutaneous primary malignancy.

Differences between ulcerated and non-ulcerated hemangiomas, a retrospective study of 465 cases.

Our purpose was to get better insight into the ulceration of hemangiomas, by comparing patient characteristics of non-ulcerated hemangiomas with hemangiomas with active or past ulceration. A retrospective analysis was performed of files of patients who visited the Radboud University Medical Centre Nijmegen (UMCN), the Netherlands, between 1997 and 2007 for one or more infantile hemangiomas. The medical records of 465 patients were reviewed.

Cardiovascular risk factors in high-need psoriasis patients and its implications for biological therapies.

Background: The associations between psoriasis and cardiovascular risk factors are reported to be stronger as psoriasis severity increases. This makes studying cardiovascular risk factors in high-need psoriasis patients, eligible for biological therapy, interesting.

Objective: To survey the prevalence of cardiovascular risk factors in high-need psoriasis patients and to compare these data to patients with other dermatological diseases.

Reduced CD26bright expression of peripheral blood CD8+ T-cell subsets in psoriatic patients.

Background: T cells have been shown to be highly relevant in psoriasis. CD26 is a novel T-cell activation marker involved in various T-cell functions, e.g.

Bone marrow mononuclear cells of MDS patients are characterized by in vitro proliferation and increased apoptosis independently of stromal interactions.

Enhanced proliferation of MDS progenitors is abrogated by increased apoptosis of their progeny in vivo. We investigated whether bone marrow mononuclear cells (BMMNC) of MDS patients also showed enhanced proliferation and apoptosis in vitro in comparison with acute myeloid leukemia (AML) and normal BM (NBM). NBM showed a decrease in the number of clusters in time due to apoptosis of clusters and due to development of clusters into colonies with low apoptotic level.

Etanercept and efalizumab treatment for high-need psoriasis. Effects and side effects in a prospective cohort study in outpatient clinical practice.

Background: Since the beginning of 2005, etanercept and efalizumab are officially registered and reimbursed for the treatment of recalcitrant psoriasis in The Netherlands.

Objective: The evaluation of the efficacy, safety and adverse events of etanercept and efalizumab treatment in daily practice.

Methods: A prospective cohort study was carried out for patients treated with etanercept or efalizumab between February 2005 and March 2006.

Heparan sulfate on activated glomerular endothelial cells and exogenous heparinoids influence the rolling and adhesion of leucocytes.

Background: Proliferative glomerulonephritides are characterized by the influx of leucocytes. Heparan sulfate (HS) plays an important role in the recruitment, rolling and firm adhesion of leucocytes to activated endothelium. Recently, we have shown the importance of HS on activated mouse glomerular endothelial cells (mGEnC-1) for the firm adhesion of leucocytes in a static adhesion assay.

Isolation of FRET-positive cells using single 408-nm laser flow cytometry.

Background: Flow cytometry may be used to isolate large amounts of living, fluorescently labeled cells. Certain fluorescent labels, like enhanced cyan fluorescent protein (ECFP) and enhanced yellow fluorescent protein (EYFP), allow the assessment of direct protein-protein interaction in situ, by fluorescence resonance energy transfer (FRET). However, current flow cytometric methods either require elaborate technical adaptations or, using a single laser protocol, are hampered by background signal.

Magnetic resonance tracking of dendritic cells in melanoma patients for monitoring of cellular therapy.

The success of cellular therapies will depend in part on accurate delivery of cells to target organs. In dendritic cell therapy, in particular, delivery and subsequent migration of cells to regional lymph nodes is essential for effective stimulation of the immune system. We show here that in vivo magnetic resonance tracking of magnetically labeled cells is feasible in humans for detecting very low numbers of dendritic cells in conjunction with detailed anatomical information.

Programmed cell death is an intrinsic feature of MDS progenitors, predominantly found in the cluster-forming cells.

Objective: Bone marrows (BM) of myelodysplastic syndrome (MDS) patients show increased proliferation and premature programmed cell death (PCD) in vivo as well as in vitro. We explored the proliferative capacity and apoptotic propensity of CD34+ progenitor cells of MDS patients excluding accessory cell interference.

Materials And Methods: CD34+/CD3-/CD19- cells of 5 MDS patients and 5 normal BM were sorted as single cells into single wells and were cultured in liquid medium.

Functional characterization of beta1-integrin-positive epidermal cell populations.

Epidermal keratinocytes are heterogeneous and can be divided into stem cells (strong beta1-integrin expression) with unlimited clonogenic potential, transient amplifying cells (weaker beta1-integrin expression) with restricted proliferative capacity and terminally differentiated cells (no beta1-integrin expression) that have lost the capacity to divide. We tested the hypothesis that cell kinetic characteristics of the epidermal subpopulations differ. Single cell suspensions from small human skin punch biopsies were sorted flow cytometrically into a beta1-integrin weakly positive (dim) and strongly positive (bright) subpopulation and the clonogenic potential was compared in cell culture experiments.

Systemic treatment of psoriatic patients with bexarotene decreases epidermal proliferation and parameters for inflammation, and improves differentiation in lesional skin.

Background: Bexarotene, a novel synthetic retinoid X receptor (RXR)-selective retinoid, has been reported to have antiproliferative and apoptotic stimulating effects in cutaneous T-cell lymphoma. In benign, hyperproliferative, and retinoid sensitive disorders, such as psoriasis, bexarotene has not been evaluated so far and no information on these parameters is available.

Objective: In the present study, immunohistochemical parameters for proliferation, differentiation, inflammation, and apoptosis were investigated in a group of bexarotene-treated psoriatic patients.

An automated multi well cell track system to study leukocyte migration.

Design of automated image processing systems to determine migration characteristics of individual cells is not trivial. Every test sample requires separate recording and the analysis of individual cell tracks in two- or three-dimensional migration systems by time-lapse microscopy is extremely laborious. Here, we describe a new Automated Cell Track System (ACTS).