AescuLabor Hamburg

Hamburg, Germany

AescuLabor Hamburg

Hamburg, Germany
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Fuchs T.,University of Mannheim | Puellmann K.,Aesculabor Hamburg | Emmert A.,University of Gottingen | Fleig J.,Mannheim University of Applied Sciences | And 7 more authors.
Biochemical and Biophysical Research Communications | Year: 2015

Recent evidence indicates constitutive expression of a recombinatorial TCRαβ immune receptor in mammalian monocytes and macrophages. Here, we demonstrate in vitro that macrophage-TCRβ repertoires are modulated by atherogenic low density cholesterol (LDL) and high-density cholesterol (HDL). In vivo, analysis of freshly obtained artery specimens from patients with severe carotid atherosclerosis reveals massive abundance of TCRαβ+ macrophages within the atherosclerotic lesions. Experimental atherosclerosis in mouse carotids induces accumulation of TCR bearing macrophages in the vascular wall and TCR deficient rag-/- mice have an altered macrophage-dependent inflammatory response. We find that the majority of TCRαβ bearing macrophages are localized in the hot spot regions of the atherosclerotic lesions. Advanced carotid artery lesions express highly restricted TCRαβ repertoires that are characterized by a striking usage of the Vβ22 and Vβ16 chains. This together with a significant degree of interindividual lesion repertoire sharing suggests the existence of atherosclerosis-associated TCRαβ signatures. Our results implicate the macrophage-TCRαβ combinatorial immunoreceptor in atherosclerosis and thus identify an as yet unknown adaptive component in the innate response-to-injury process that underlies this macrophage-driven disease. © 2014 Elsevier Inc. All rights reserved.

Nebe T.,Institute For Transfusionsmedizin | Bentzien F.,Universitatsklinikum Hamburg Eppendorf | Bruegel M.,Klinische Chemie und Molekulare Diagnostik Universitatsklinikum Leipzig | Fiedler G.M.,Klinische Chemie und Molekulare Diagnostik Universitatsklinikum Leipzig | And 7 more authors.
LaboratoriumsMedizin | Year: 2011

The analysis of blood cell count including differential, is the most frequent laboratory test and has still essential diagnostic value in the diagnosis of primary or secondary diseases of the hematopoietic system. The interpretation is based on a comparison with age matched reference intervals, despite the fact that a comparison with the patients own preceding values allows a more precise statement. In the present study, blood counts and differential were performed in 1158 healthy males and females with an age ranging from 16 to 75 years were investigated using current hematology systems. The donors were examined by personnel physicians and those examining blood donors in transfusion medicine and in addition were asked via standardized questionnaire. The study resulted in reference ranges for the complete blood count, the differential blood count and reticulocytes. For several analytes, age-, gender- or analyzerspecific reference ranges were obtained. We found an age dependent decrease of the erythrocyte concentration and an increase for MCH and MCV as well as for basophils. These findings could be important for the dignosis of diseases of the elderly like myeloproliferative diseases (MPN) and myelodysplasias (MDS). Gender specific changes could be shown for the hemoglobulin-, the erythrocyte- and reticulocyte concentration, as well as for hematocrit and MCHC, being reduced in females. On the other hand, females showed significant higher levels for platelets and leukocytes, based on an increase of neutrophils and lymphocytes. The leukocytosis of smokers was confirmed for neutrophils and lymphocytes but lower than one could expect from recent studies. A multicentric study shows a broader distribution compared to unicentric data but this probably better reflects the reality and improves the applicability of the reference ranges. © 2011 by Walter de Gruyter.

PubMed | University of Mannheim, University of Gottingen, University of Heidelberg and Aesculabor Hamburg
Type: Journal Article | Journal: Immunobiology | Year: 2015

Recent evidence indicates the presence of macrophage subpopulations that express the TCR in two major inflammatory diseases, tuberculosis and atherosclerosis. Inflammation is also a well-established attribute of cancer progression and macrophages are one of the major immune cells that infiltrate tumors. Here, we demonstrate that the macrophage-TCR is expressed in the tumor microenvironment of human and murine malignancies. We identify TCR

Tappe D.,Bernhard Nocht Institute for Tropical Medicine | Slesak G.,Tropenklinik Paul Lechler Hospital | Perez-Giron J.V.,Heinrich Pette Institute | Schafer J.,Tropenklinik Paul Lechler Hospital | And 6 more authors.
Clinical and Vaccine Immunology | Year: 2015

Sarcocystis nesbitti is a parasite responsible for a biphasic eosinophilic febrile myositis syndrome in two recent outbreaks in Malaysia. We demonstrate Th2 cytokine polarization in infected travelers, an overall cytokine production decrease in the early phase of the disease suggestive of initial immunosuppression, and elevated levels of proinflammatory and chemotactic cytokines in the later myositic phase. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

PubMed | Medizinische Klinik 1, AescuLabor Hamburg, Goethe University Frankfurt, Tropenklinik Paul Lechler Hospital and 2 more.
Type: Journal Article | Journal: Clinical and vaccine immunology : CVI | Year: 2015

Sarcocystis nesbitti is a parasite responsible for a biphasic eosinophilic febrile myositis syndrome in two recent outbreaks in Malaysia. We demonstrate Th2 cytokine polarization in infected travelers, an overall cytokine production decrease in the early phase of the disease suggestive of initial immunosuppression, and elevated levels of proinflammatory and chemotactic cytokines in the later myositic phase.

Gezsi A.,Semmelweis University | Budde U.,AescuLabor Hamburg | Deak I.,Corvinus University of Budapest | Nagy E.,Semmelweis University | And 6 more authors.
Journal of Thrombosis and Haemostasis | Year: 2010

Background: von Willebrand disease (VWD) Vicenza is characterized by low plasma von Willebrand factor (VWF) levels, the presence of ultra-large (UL) VWF multimers and less prominent satellite bands on multimer gels, and the heterozygous amino acid substitution R1205H in the VWF gene. The pathogenesis of VWD Vicenza has been elusive. Accelerated clearance is implicated as a cause of low VWF level. Objectives: We addressed the question, whether the presence of ultra-large multimers is a cause, or a result of accelerated VWF clearance, or whether it is an unrelated phenomenon. Patients/methods: We studied the detailed phenotype of three Hungarian patients with VWD Vicenza, expressed the mutant VWF-R1205H in 293T cells and developed a mathematical model to simulate VWF synthesis and catabolism. Results: We found that the half-life of VWF after DDAVP was approximately one-tenth of that after the administration of Haemate P, a source of exogenous wild-type (WT) VWF (0.81 ± 0.2 vs. 7.25 ± 2.38 h). An analysis of recombinant mutant VWF-R1205H showed that the biosynthesis and multimer structure of WT and mutant VWF were indistinguishable. A mathematical model of the complex interplay of VWF synthesis, clearance and cleavage showed that decreasing VWF half-life to one-tenth of normal reproduced all features of VWD Vicenza including low VWF level, ultra-large multimers and a decrease of satellite band intensity. Conclusion: We conclude that accelerated clearance alone may explain all features of VWD Vicenza. © 2010 International Society on Thrombosis and Haemostasis.

Gutensohn K.,University of Hamburg | Vossen D.,AescuLabor Hamburg | Strate A.,University of Gottingen | Kersten J.F.,University of Hamburg | And 2 more authors.
International Journal of Laboratory Hematology | Year: 2013

Introduction: Anti-cardiolipin and β2-glycoprotein I antibodies represent important diagnostic parameters in routine hematology. In this study, five different automated, semi-automated, and manual immunoassays detecting IgG/IgM anti-cardiolipin and anti-β2-glycoprotein I antibodies were tested. Methods: A total of 162 samples from women with a history of miscarriage were recruited from 110 different G&O outpatient centers in Germany. Results: For both anti-cardiolipin and anti-β2-glycoprotein I antibodies, considerable differences in the percentage of positive results were seen between all five methods, and itemization of all positive test results revealed a poor accordance. These findings were confirmed by Cohen's kappa coefficients. Conclusion: Our study revealed a moderate to poor accordance between five different test systems for anti-cardiolipin and anti-β2-glycoprotein I antibodies. Such deviations may result in clinical misinterpretation of data and may lead to wrong therapeutic consequences. Therefore, further standardization of all tests for anti-phospholipid antibodies should be achieved. © 2012 Blackwell Publishing Ltd.

Panzer S.,Medical University of Vienna | Eslam R.B.,Medical University of Vienna | Schneller A.,Medical University of Vienna | Kaider A.,Medical University of Vienna | And 5 more authors.
Thrombosis and Haemostasis | Year: 2010

Severe aortic stenosis is associated with a haemostatic abnormality that resembles acquired von Willebrand syndrome type 2. It is assumed that high shear conditions render large von Willebrand factor (VWF) multimers accessible to cleavage by ADAMTS-13. However, whether loss of these large multimers affects platelet function by impairing adhesion, aggregate formation, or both has not been evaluated in clinical studies. We prospectively enrolled 47 patients with severe aortic stenosis, and studied them prior to aortic valve surgery and at a median of six months after valve replacement. We investigated levels of large VWF multimers, platelet function under high shear conditions, and residual response to suboptimal concentrations of ADP to express P-selectin. As expected, there was a significant reduction of VWF large multimers before surgery that resolved thereafter in most patients (p<0.0001). The closure time of the ADP cartridge of the PFA-100 was also corrected in most patients after the operation (p<0.0001). We used the cone and plate(let) analyser Impact-R to differentiate between adhesion and aggregation. Both adhesion (p=0.03) and ADP-inducible platelet aggregation (p=0.002) improved considerably after valve replacement. Consequently, ADP-inducible expression of P-selectin was higher after valve replacement (p=0.001). We conclude that reduced levels of large VWF multimers associated with aortic stenosis lead to impairment of both adhesion and, especially, ADP-inducible platelet aggregation. © Schattauer 2010.

Meyer A.L.,University of Leipzig | Malehsa D.,Hannover Medical School | Budde U.,AescuLabor Hamburg | Bara C.,Hannover Medical School | And 2 more authors.
JACC: Heart Failure | Year: 2014

Objectives: The aim of this study was to determine whether differences in continuous flow left ventricular assist devices (LVADs) may lead to differences in the von Willebrand profile and the occurrence of bleeding and thromboembolic events. Background: The HeartMate II (Thoratec Corp., Pleasanton, California) and HeartWare Ventricular Assist Device (HVAD) (HeartWare, Inc., Framingham, Massachusetts) systems are the most frequently implanted LVADs worldwide. In all patients with an axial-flow HeartMate II, acquired von Willebrand syndrome (AvWS) due to the loss of large molecular weight multimers was found. The large molecular weight multimers of the von Willebrand factor (vWF) play a key role in primary hemostasis through interactions with platelets. Methods: This was a retrospective study of the vWF profile and incidence of bleeding and thromboembolic events in 102 patients receiving the HeartMate II (n= 51) and HVAD (n= 51). Between January 2003 and December 2010, vWF testing was performed in 102 of 175 consecutive patients after LVAD implantation. Results: AvWS was found in all patients, demonstrated by a decrease in the high molecular weight multimers of vWF to 30±14% in HeartMate II patients and 34 ± 13% in patients with an HVAD. Significant predictors of vWF antigen included age (p= 0.011), number of days on the device (p= 0.035), C-reactive protein (p< 0.001), and blood group (p= 0.007). Bleeding and thromboembolic event rates were similar. However, lower fractions of vWF antigen and high molecular weight multimers did not correlate with the rate of bleeding complications or thromboembolic events. Conclusions: AvWS developed in all patients after centrifugal or axial flow pump implantation. Different patterns of AvWS wereseen between the devices as well as individually. However, the complication rates after implantation were similar. © 2014 American College of Cardiology Foundation.

Meyer A.L.,Hannover Medical School | Malehsa D.,Hannover Medical School | Bara C.,Hannover Medical School | Budde U.,AescuLabor Hamburg | And 3 more authors.
Circulation: Heart Failure | Year: 2010

Background - Rotary blood pumps used as left ventricular assist devices (LVADs) allow for long-term support and may become suitable alternatives to heart transplantation. Effects of this technology on the coagulation system are not completely understood, leading to controversial anticoagulation protocols. Thus, we investigated the primary hemostasis in patients with chronic LVAD therapy. Methods and Results - Twenty-six outpatients received axial flow LVAD (HeartMate II; Thoratec) for a median support time of 4.5 months. In a cross-sectional protocol, platelet aggregation in response to ADP and epinephrine, von Willebrand antigen (vWF:AG), and collagen-binding capacity (vWF:CB) were obtained. Von Willebrand factor (vWF) multimer analyses were performed, and patients were screened for bleeding events. This analysis was repeated after removal of the device for transplantation or recovery (n=12) and after a median of 15.5 months in ongoing patients (n=11). In all patients on devices, severe impairment of platelet aggregation as well as a loss of large vWF multimers were found. In 10 patients, a decreased vWF:CB/vWF:AG ratio was observed. Bleeding episodes occurred with an incidence of 0.17 per patient-year. After removal of the device, normal patterns of platelet aggregation, multimer analysis, and vWF:CB/vWF:AG ratio were recorded. In the second analysis of ongoing patients, impairment of platelet aggregation and loss of large vWF multimers were verified. Conclusions - A diagnosis of von Willebrand syndrome type 2 was established in all patients after LVAD implantation, and bleeding events confirmed this finding. Reversibility of this condition was found after removal of the device. (Circ Heart Fail. 2010;3:675-681.). © 2010 American Heart Association, Inc.

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