Heterogeneous expression of cell adhesion molecules by endothelial cells in ARDS

ARDS (acute respiratory distress syndrome) can be associated with septic shock and multiple organ failure caused by an uncontrolled systemic inflammatory response to Gram-negative bacterial infection. While in animal models the key role of the endothelial adhesion molecules ICAM-1, E-selectin, and VCAM in ARDS has been extensively studied, there are scarcely any corresponding pathomorphological studies of human lung tissue. Hence, little is known about whether there is a comparable, or even heterogeneous, expression pattern of these molecules in the human pulmonary vasculature. This study was therefore undertaken to investigate the immunohistochemical expression of the constitutively expres…

Pulmonary haemangiolymphangioma – a new entity of pulmonary vascular tumours?

Extreme Methylation Values of Imprinted Genes in Human Abortions and Stillbirths

Imprinted genes play an important role in fetal and placental development. Using quantitative bisulfite pyrosequencing assays, we determined the DNA methylation levels at two paternally methylated (H19 and MEG3) and four maternally methylated (LIT1, NESP55, PEG3, and SNRPN) imprinted regions in fetal muscle samples from abortions and stillbirths. Two of 55 (4%) spontaneous abortions and 10 of 57 (18%) stillbirths displayed hypermethylation in multiple genes. Interestingly, none of 34 induced abortions had extreme methylation values in multiple genes. All but two abortions/stillbirths with multiple methylation abnormalities were male, indicating that the male embryo may be more susceptible t…

Expression of endothelial cell adhesion molecules on heart valves: up-regulation in degeneration as well as acute endocarditis

Inflammatory cytokines such as interleukin-1 (IL-1) and tumour necrosis factor-alpha (TNF-alpha), as well as shear stress, cause endothelial cells (ECs), to undergo not only functional alterations but also structural reorganizations, which contribute to vascular leakage. Like ECs of the human aorta, ECs on heart valves are exposed to extreme shear stress. However, while ECs expression of cell adhesion molecules (CAMs) in large vessels has been widely studied, it seems that there are no such studies on ECs of heart valves, although this knowledge might be important for our understanding of the aetiological aspects of local inflammatory responses. Using immunohistochemistry, this study charac…

Genetic Deletion of JNK1 and JNK2 Aggravates the DSS-Induced Colitis in Mice

The c-Jun N-terminal kinases (JNKs) are considered as novel targets for therapy of inflammatory bowel diseases (IBD). However, the relevant JNK isoforms have to be elucidated. Here, we analyze the individual contribution of the JNK1 and JNK2 isoforms in a dextran sulfate sodium (DSS) model of experimental colitis. JNK1 and JNK2 knockout mice (JNK1 ko, JNK2 ko) and their wild-type controls (WT1, WT2) received three cycles of DSS treatment, each consisting of 1.7% DSS for 5 days, followed by 5 days with water. Animals were daily evaluated by a disease activity index (DAI) comprising measurement of body weight, estimation of stool consistency, and test for occult blood/gross rectal bleeding. A…

Quantitative methylation analysis of developmentally important genes in human pregnancy losses after ART and spontaneous conception.

To study possible effects of assisted reproductive technologies (ART) on epigenetic reprogramming, we have analyzed the DNA methylation levels of differentially methylated regions (DMRs) of seven imprinted genes (H19, MEG3, LIT1, MEST, NESP55, PEG3 and SNRPN) as well as the promoter regions of the pluripotency gene NANOG and the tumor suppressor gene APC in chorionic villus samples (CVS) of 42 spontaneous miscarriages and stillbirths after ART and 29 abortions/stillbirths after spontaneous conception. We did not find an increased rate of faulty methylation patterns after ART, but significant and trend differences (ROC curve analysis, Wilcoxon test) in the methylation levels of LIT1 (P = 0.0…

Clinical and morphological characteristics in Streptococcus bovis endocarditis: a comparison with other causative microorganisms in 177 cases

Aim—To compare the clinical and morphological characteristics of patients with Streptococcus bovis endocarditis with those of patients with endocarditis caused by other microorganisms. Methods—177 consecutive patients (Streptococcus bovis, 22; other streptococci, 94; staphylococci, 44; other, 17) with definite infective endocarditis according to the Duke criteria were included. All patients underwent transthoracic and transoesophageal echocardiography. In 88 patients, findings from surgery/necropsy were obtained. Results—S bovis endocarditis was associated with older patients, with a higher mortality (p = 0.04), and with a higher rate of cardiac surgery (p < 0.001) than other microorganisms…

Diagnosis of culture-negative endocarditis: The role of the Duke criteria and the impact of transesophageal echocardiography

Abstract Background The Duke criteria have been shown to be more sensitive than the von Reyn criteria in the diagnosis of culture-positive endocarditis but to date have not been fully validated for culture-negative endocarditis (CNE). The aim of this study was (1) to compare the diagnostic accuracy of the Duke criteria versus clinical judgment and the von Reyn criteria in CNE and (2) to assess the diagnostic impact of transesophageal echocardiography (TEE) on the Duke criteria in CNE. Methods The study group consisted of 49 patients with suspected CNE in whom the presence (n = 32) or absence (n = 17) of endocarditis was confirmed by surgery, autopsy, or both. All patients underwent transtho…

Oral administration of taurolidine ameliorates chronic DSS colitis in mice.

Taurolidine (TRD) has antimicrobial and anti-inflammatory properties. However, the anti-inflammatory effects of TRD in inflammatory bowel diseases (IBD) have not been investigated. Here, we have analyzed the toxicity of TRD after oral long-term application in mice and examined the impact of oral TRD in a dextran sulfate sodium (DSS) model of experimental colitis. Female C57/BL6 mice received TRD in various concentrations (0.1% to 0.4%) for 60 days. Toxicity was evaluated by use of a disease activity index (DAI) and histological examination of major metabolic organs. Furthermore, the impact of 0.2% TRD on a chronic DSS colitis was examined by daily DAI, histological crypt damage score (CDS),…

Expression of the endothelial markers PECAM-1, vWf, and CD34 in vivo and in vitro.

EC culture models are essential to study pathological alterations of endothelial cells (ECs) in pulmonary vascular diseases under standardized conditions. Nevertheless, little is known about the spectrum of alterations of vessel-specific endothelial phenotypes in monolayer cultures. For the comparative study of endothelial markers in vivo and in vitro we investigated immunohistochemically the expression of PECAM-1, vWf, and CD34 by pulmonary ECs in vivo and in stimulated/unstimulated human umbilical vein endothelial cells (HU-VEC) and human pulmonary microvascular endothelial cells (HPMEC). In vivo, vessel type-specific expression patterns were found for vWf and CD34, while PECAM-1 was homo…

Comparative Study of Adhesion Molecule Expression in Cultured Human Macro- and Microvascular Endothelial Cells

Culture systems as models for disease are only valid as long as they are comparable to in vivo conditions. The phenotype of cultured endothelial cells (ECs) has only been sporadically compared to the corresponding phenotype in vivo. Thus, we compared by immunolocalization the endothelial expression of ICAM-1, VCAM, and E-selectin in vivo in stimulated/unstimulated human umbilical vein endothelial cells (HUVEC) as a model for macrovascular ECs and stimulated/unstimulated HPMEC (human pulmonary microvessel endothelial cells) as a model for pulmonary microvascular ECs with that in human lungs in vivo (normal and ARDS). Proinflammatory stimuli in vitro were used to stimulate conditions relevant…

Primäres Leiomyosarkom der Pulmonalarterie: Inzidenz, Diagnostik und Therapie

Leiomyosarkome des Herzens und der grosen Gefase sind sehr seltene hochmaligne Tumoren, die meist rasch zum Tode fuhren.¶ Wir berichten uber einen 31-jahrigen Patienten mit einem von der Pulmonalklappe ausgehenden Leiomyosarkom, das beide Pulmonalarterien und den Ausflusstrakt des rechten Ventrikels miteinbezog. Infolge der raschen Diagnosestellung und nachfolgenden radikalen Resektion ist der Patient nach mehr als 5 Jahren weiterhin tumorfrei. Nur die fruhzeitige Diagnose und komplette chirurgische Excision konnen die Uberlebenschance fur Patienten mit Pulmonalissarkomen erhohen.

Knock out der c-Jun N-terminalen Kinase 2 (JNK2) aggraviert die Entwicklung der chronischen DSS-Colitis unabhängig von der intestinalen Zytokin-Expression

Background The c-Jun N-terminal kinase 2 (JNK2) is involved in signal transduction of inflammatory bowel diseases (IBD) and regulates the expression of pro-inflammatory cytokines. For this reason, JNK2 is considered as novel target for IBD therapy. The aim of this study was 1.) to examine the function of JNK2 applying a low dose Dextran Sulfate Sodium (DSS) model of chronic experimental colitis in JNK2 knock out mice and 2.) to analyze the expression of JNK2 dependent cytokines. Material and Methods: For induction of a mild chronic colitis, female JNK2 knockout mice (JNK2 ko) and their wildtype controls (WT2) received three cycles of DSS treatment, each consisting of 1.0 % DSS for 5 days, f…