Small poly-L-lysines improve cationic lipid-mediated gene transfer in vascular cells in vitro and in vivo.

The potential of two small poly-L-lysines (sPLLs), low molecular weight sPLL (LMW-L) containing 7-30 lysine residues and L18 with 18 lysine repeats, to enhance the efficiency of liposome-mediated gene transfer (GT) with cationic lipid DOCSPER [1,3-dioleoyloxy-2-(N(5)-carbamoyl-spermine)-propane] in vascular smooth muscle cells (SMCs) was investigated. Dynamic light scattering was used for determination of particle size. Confocal microscopy was applied for colocalization studies of sPLLs and plasmid DNA inside cells.

Acetylsalicylic acid (ASA) blocks influenza virus propagation via its NF-kappaB-inhibiting activity.

Influenza is still one of the major plagues worldwide. The statistical likeliness of a new pandemic outbreak highlights the urgent need for new and amply available antiviral drugs. We and others have shown that influenza virus misuses the cellular IKK/NF-kappaB signalling pathway for efficient replication suggesting that this module may be a suitable target for antiviral intervention.

Influenza A virus NS1 protein activates the PI3K/Akt pathway to mediate antiapoptotic signaling responses.

Recently we have shown that influenza A virus infection leads to activation of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway and that this cellular reaction is dependent on the expression of the viral nonstructural protein 1 (NS1). These data also suggested that PI3K activation confers a virus-supporting activity at intermediate stages of the infection cycle. So far it is not known which process is regulated by the kinase that supports virus replication.

Bivalent role of the phosphatidylinositol-3-kinase (PI3K) during influenza virus infection and host cell defence.

Infections with influenza A viruses result in the activation of a variety of intracellular signalling pathways. Recent findings suggest that in response to double-stranded RNA (dsRNA), which is commonly used as a mimic for accumulating viral RNA, the phosphatidylinositol-3-kinase (PI3K) is activated and mediates activation of the transcription factor interferon regulatory factor 3 (IRF-3). Thus, we investigated the function of PI3K during influenza virus infection.

A model of biological motion perception from configural form cues.

Biological motion perception is the compelling ability of the visual system to perceive complex human movements effortlessly and within a fraction of a second. Recent neuroimaging and neurophysiological studies have revealed that the visual perception of biological motion activates a widespread network of brain areas. The superior temporal sulcus has a crucial role within this network.

Ringing the alarm bells: signalling and apoptosis in influenza virus infected cells.

Small RNA viruses such as influenza viruses extensively manipulate host-cell functions to support their replication. At the same time the infected cell induces an array of defence mechanisms to fight the invader. These processes are mediated by a variety of intracellular signalling cascades.

Treatment effects of high-dose antithrombin without concomitant heparin in patients with severe sepsis with or without disseminated intravascular coagulation.

Background: Disseminated intravascular coagulation (DIC) is a serious complication of sepsis that is associated with a high mortality.

Objectives: Using the adapted International Society on Thrombosis and Haemostasis (ISTH) diagnostic scoring algorithm for DIC, we evaluated the treatment effects of high-dose antithrombin (AT) in patients with severe sepsis with or without DIC.

Patients And Methods: From the phase III clinical trial in severe sepsis (KyberSept), 563 patients were identified (placebo, 277; AT, 286) who did not receive concomitant heparin and had sufficient data for DIC determination.

GABAergic neurons: gate masters of the amygdala, mastered by dopamine.

A hyperdopaminergic state, such as stress, is associated with an increase in affective behavior. In this issue of Neuron, Marowsky and colleagues identify two clusters of paracapsular intercalated GABA neurons in amygdala slice preparations of GAD67-GFP mice. These GABA neurons mediate inhibition from cortical afferents to both the major input and output station of the amygdala, are inhibited during action of dopamine via D1 receptors, and are thus likely to represent important cellular players during dopaminergic disinhibition related to increased affective behavior.

Comparative genomic hybridization in cartilaginous tumors.

Genetic aberrations in cartilaginous tumors have not yet been well characterized. We analyzed the molecular-chromosomal aberrations in 10 chondrosarcomas (four Grade-3 tumors, four Grade-2 tumors and two Grade-1 tumors) and in three benign cartilaginous tumors (two enchondromas and one chondromyxoid fibroma). Genomic imbalances were detected in 9 out of 10 cases of chondrosarcomas.

Cyclic strain influences the expression of the vascular endothelial growth factor (VEGF) and the hypoxia inducible factor 1 alpha (HIF-1alpha) in tendon fibroblasts.

Neovascularization is involved in beneficial and detrimental processes of tendon pathology. We investigated the influence of repetitive motion on the expression of the most important angiogenic factor, the vascular endothelial growth factor (VEGF) in the 3T3 NIH fibroblast cell line and in cultures of rat Achilles tendon fibroblasts. Monolayers of subconfluently grown cells were stretched in rectangular silicone dishes with cyclic uniaxial movement.

Proprioception with bicondylar sledge prostheses retaining cruciate ligaments.

The current study was designed to evaluate the proprioceptive performance of the knee after implantation of bicondylar sledge prostheses in comparison with contralateral knees and knees of healthy control subjects. After implantation of a sledge prosthesis in the medial and lateral condyles of a knee retaining all ligaments, 15 patients were evaluated clinically and by proprioceptive testing. Clinical examination was done using common scoring systems.

ProSAP/Shank postsynaptic density proteins interact with insulin receptor tyrosine kinase substrate IRSp53.

The ProSAP/Shank family of multidomain proteins of the postsynaptic density (PSD) can either directly or indirectly interact with NMDA-type and metabotropic glutamate receptors and the actin-based cytoskeleton. In a yeast two hybrid screen utilizing a proline-rich domain that is highly conserved among the ProSAP/Shank family members, we isolated several cDNA clones coding for the insulin receptor substrate IRSp53. The specificity of this interaction was confirmed in transfected COS cells.

Population-based genetic alterations in Ewing's tumors from Japanese and European Caucasian patients.

Background: The incidence of Ewing's tumors (ETs) is lower in Asians or African-Americans than in Caucasians.

Patients And Methods: Japanese ETs were available for analysis of chromosomal aberrations by comparative genomic hybridization (n = 16) and for expression of chimeric EWS transcripts by reverse-transcriptase polymerase chain reaction (n = 11). These results in Japanese patients were compared with those of 62 ETs in European Caucasian patients registered in the European Intergroup Cooperative Ewing's Sarcoma Study.

Proprioceptive function, clinical results, and quality of life after unicondylar sledge prostheses.

Objective: Evaluation of proprioceptive performance and quality of life after implantation of unicondylar sledge knee prostheses in comparison with normal control subjects.

Design: A total of 17 patients were examined after implantation of unicondylar sledge prostheses. Clinical examination was performed, quality of life was assessed, and proprioceptive performance was examined.

ProSAP/Shank proteins - a family of higher order organizing molecules of the postsynaptic density with an emerging role in human neurological disease.

The postsynaptic density (PSD) is a specialized electron-dense structure underneath the postsynaptic plasmamembrane of excitatory synapses. It is thought to anchor and cluster glutamate receptors exactly opposite to the presynaptic neurotransmitter release site. Various efforts to study the molecular structure of the PSD identified several new proteins including membrane receptors, cell adhesion molecules, components of signalling cascades, cytoskeletal elements and adaptor proteins with scaffolding functions to interconnect these PSD components.

An epicardial cyst in a child.

An 8-year-old girl, without any previous medical history, presented with a first short syncope. Physical examination was unremarkable. Transthoracic echocardiography revealed a thin-walled, echo-free cystic structure adjacent to the posterior wall of the left ventricle, and compressing it moderately.

A long-term follow-up study after retro-orbital irradiation for Graves' ophthalmopathy.

Purpose: The aim of this retrospective analysis was to find out whether low-dose radiation, which is used in the treatment of Graves' ophthalmopathy, could cause radiation-induced cancer, which would in turn adversely affect the survival of the irradiated population and cause an increase in the cancer-specific death rate.

Methods And Materials: From 1963 to 1978, 250 patients received bilateral orbital irradiation for a progressive Graves' ophthalmopathy. Median age was 49 years.

Alteration of fracture stability influences chondrogenesis, osteogenesis and immigration of macrophages.

Mechanical conditions at the fracture line determine the mode of fracture healing (osteonal versus non-osteonal bone union). The aim of this study was to investigate the influence of differing degrees of fracture stability on the time course of chondrogenesis, enchondral ossification and immigration of macrophages into the fracture callus. Using a fracture model of the rat's tibia, histological (Azan staining), immunohistological (antibodies directed against the macrophage-specific surface antigen ED2), and molecular biological techniques (expression of the mRNA of the cartilage-specific collagen IX, osteocalcin - a marker for mature osteoblasts - and the macrophage-specific macrosialin) were employed.

Inflammatory markers in major depression and melancholia.

Background: There is evidence that patients with major depression (MD) also suffer an inflammatory immune reaction. However, the results remain ambiguous. This could be due to the psychiatrically heterogeneous patient samples investigated in many published studies.

Impact of radiofrequency catheter ablation of accessory pathways on the frequency of atrial fibrillation during long-term follow-up; high recurrence rate of atrial fibrillation in patients older than 50 years of age.

Aims: Atrial fibrillation represents a frequent and potentially life-threatening arrhythmia in patients with accessory atrioventricular pathways. Radiofrequency ablation has become the curative treatment of first choice for these patients. Investigations after successful surgical pathway dissection reported an almost complete elimination of paroxysmal atrial fibrillation.

A new clamping technique for biomechanical testing of tendons in small animals. aprobst@uni-muenster.de.

When biomechanical properties of tendons are studied, the technique of clamping the tendons in the testing machine presents a methodological challenge, especially when murine tendons are examined. These short tendons tend to rupture at the transition line to the fixation, leading to false interpretations. Therefore a new clamping technique for investigation of healthy murine Achilles tendons (n = 50) was developed, in which the intramuscular tendon fibers were fixed between two paper strips and the calcaneus was wedged into a conical slot in a wooden block and then mounted in the testing machine (n = 20).

Liver bridging techniques in the treatment of acute liver failure.

The introduction of orthotopic liver transplantation in the management of acute liver failure has dramatically increased the survival rates of patients at the cost of removing the patient's native liver and life-long dependence on immunosuppression. However, it is well known that in many patients with acute liver failure the diseased liver has the potential to recover. Death in these patients is often due to increased intra-cranial pressure or infection.

Monoclonality in normal epithelium and in hyperplastic and neoplastic lesions of the breast.

The clonal nature of neoplastic lesions such as invasive breast cancer and ductal carcinoma in situ (DCIS) has been widely proven by several proliferative, genetic or other malignancy-associated markers. The aim of this study is to clarify whether benign hyperplastic lesions such as ductal hyperplasia of usual type (DH) and papilloma can be distinguished from neoplastic lesions such as DCIS by X-chromosome inactivation analysis. Clonal analysis was performed using a polymerase chain reaction-based assay for non-random X-chromosome inactivation of the human androgen receptor gene (HUMARA).

Controlled vasoregulation of postischemic liver microcirculation--a therapeutic approach.

One of the changes produced by ischemia and reperfusion is endothelin (ET)-mediated constriction of the hepatic vascular bed. This leads to microcirculatory disturbances and reduced blood flow, thereby causing local hypoxia and liver damage. Our aim was to induce stepwise changes of microvascular vessel diameters so as to define the best protective vessel width that could be produced by drug therapy and thereby to minimize ischemia/reperfusion injury.