Involvement of CD252 (CD134L) and IL-2 in the expression of cytotoxic proteins in bacterial- or viral-activated human T cells.

Regulation of cytotoxic effector molecule expression in human CTLs after viral or bacterial activation is poorly understood. By using human autologous dendritic cells (DCs) to prime T lymphocytes, we found perforin only highly up-regulated in virus- (HSV-1, vaccinia virus) but not in intracellular bacteria- (Listeria innocua, Listeria monocytogenes, Mycobacterium tuberculosis, Chlamydophila pneumoniae) activated CTLs. In contrast, larger quantities of IFN-gamma and TNF-alpha were produced in Listeria-stimulated cultures.

Chlamydophila pneumoniae derived from inclusions late in the infectious cycle induce aponecrosis in human aortic endothelial cells.

Background: Atherosclerosis is still the leading cause of death in the western world. Besides known risk factors studies demonstrating Chlamydophila pneumoniae (C. pneumoniae) to be implicated in the progression of the disease, little is known about C.

Perforin enhances the granulysin-induced lysis of Listeria innocua in human dendritic cells.

Background: Cytotoxic T lymphocytes (CTL) and natural killer (NK) cells play an essential role in the host defence against intracellular pathogens such as Listeria, and Mycobacteria. The key mediator of bacteria-directed cytotoxicity is granulysin, a 9 kDa protein stored in cytolytic granules together with perforin and granzymes. Granulysin binds to cell membranes and is subsequently taken up via a lipid raft-associated mechanism.

Expression, processing and transcriptional regulation of granulysin in short-term activated human lymphocytes.

Background: Granulysin, a cytotoxic protein expressed in human natural killer cells and activated T lymphocytes, exhibits cytolytic activity against a variety of intracellular microbes. Expression and transcription have been partially characterised in vitro and four transcripts (NKG5, 519, 520, and 522) were identified. However, only a single protein product of 15 kDa was found, which is subsequently processed to an active 9 kDa protein.

Is silicone oil optic neuropathy caused by high intraocular pressure alone? A semi-biological model.

Background: Silicone oil endotamponade is used for the repair of complicated retinal detachments. Cataract, glaucoma and corneal endothelial dysfunction are the most frequent complications of silicone oil tamponade. Clinical and histopathological studies have revealed that silicone oil can penetrate into the optic nerve and into the brain.

Evaluation of an anatomic model of the paranasal sinuses for endonasal surgical training.

Objectives: To assess the suitability of a new anatomic model of the paranasal sinuses for endonasal surgical training.

Study Design: Prospective observational pilot study.

Methods: A new anatomic model of the paranasal sinuses was developed by the Department of Anatomy at the University of Zurich.

Cholesterol in negatively charged lipid bilayers modulates the effect of the antimicrobial protein granulysin.

The release of granulysin, a 9-kDa cationic protein, from lysosomal granules of cytotoxic T lymphocytes and natural killer cells plays an important role in host defense against microbial pathogens. Granulysin is endocytosed by the infected target cell via lipid rafts and kills subsequently intracellular bacteria. The mechanism by which granulysin binds to eukaryotic and prokaryotic cells but lyses only the latter is not well understood.

Polyurethane elastomer: a new material for the visualization of cadaveric blood vessels.

A multitude of various materials are available for the visualization of cadaveric vessels, ranging from natural materials like gelatin and latex to synthetic materials like silicone rubber or acrylates. To achieve a detailed overview of the vascular architecture in microvascular studies in experimental flap surgery, the injected material should have low viscosity to assure perfusion of even the smallest vessels. In addition, the material ideally should have either no or only minimal shrinkage, and should harden within a reasonable time, but retain sufficient elasticity and resistance to withstand tearing off the delicate vessels during subsequent dissection or casting.

The anatomy of the sphenopalatine artery for the endoscopic sinus surgeon.

Background: This study was performed to determine the variations in the branching pattern of the sphenopalatine artery medial to the crista ethmoidalis. Seventy-seven cadaver head sides that had been sectioned sagittally in the midline with their septum removed were used after injecting pink latex to highlight the arterial vessels.

Methods: The mucosa from the middle meatus from the level of the basal lamella was removed until the artery and its branches were seen and then was examined under the microscope to identify the position of the arterial branches.

Lack of neprilysin suffices to generate murine amyloid-like deposits in the brain and behavioral deficit in vivo.

Accumulation of the beta-amyloid peptide (Abeta) in the brain is a major pathological hallmark of Alzheimer's disease (AD), leading to synaptic dysfunction, neuronal death, and memory impairment. The levels of neprilysin, a major Abeta-degrading enzyme, are decreased in AD brains and during aging. Because neprilysin cleaves Abeta in vivo, its down-regulation may contribute to the pathophysiology of AD.

Human dendritic cells process and present Listeria antigens for in vitro priming of autologous CD4+ T lymphocytes.

The role of human dendritic cells (DC) in the immune response toward intracellularly growing Listeria was analyzed under in vitro conditions using several morphological and functional methods. DC incubated with Listeria innocua and L. monocytogenes, respectively, readily phagocytosed the bacteria.

Central necrosis in isolated hypoxic human pancreatic islets: evidence for postisolation ischemia.

A variety of explanations have been provided to elucidate the requirement of the large islet mass that is essential for a successful treatment of patients with type I diabetes by intrahepatic transplantation. The purpose of this study was to investigate islet cell survival under the effect of prolonged hypoxia and/or nutrient withdrawal, which mimics posttransplantation environment of transplanted islets in the liver. We studied the influence of 24 h of hypoxia (1% O2) in intact isolated human and rat islets as well as the effect of combined oxygen/nutrient deprivation in a mouse insulinoma cell line (MIN6).

Uptake of granulysin via lipid rafts leads to lysis of intracellular Listeria innocua.

The bacteriolytic activity of CTL is mediated by granulysin, which has been reported to kill intracellular Mycobacterium tuberculosis in dendritic cells (DC) with high efficiency. Despite that crucial effector function, the killing mechanism and uptake of granulysin into target cells have not been well investigated. To this end we analyzed granulysin binding, uptake, and the subsequent lysis of intracellular Listeria innocua in human DC.

Chlamydia pneumoniae induces aponecrosis in human aortic smooth muscle cells.

Background: The intracellular bacterium Chlamydia pneumoniae is suspected to play a role in formation and progression of atherosclerosis. Many studies investigated cell death initiation versus inhibition by Chlamydia pneumoniae in established cell lines but nothing is known in primary human aortic smooth muscle cells, a cell type among others known to be involved in the formation of the atherosclerotic plaque. Type of cell death was analyzed by various methods in primary aortic smooth muscle cells after infection with Chlamydia pneumoniae to investigate a possible pathogenic link in atherosclerosis.

Listeria species escape from the phagosomes of interleukin-4-deactivated human macrophages independent of listeriolysin.

Listeria monocytogenes is the causative agent of infections like sepsis and meningitis, especially in immunocompromised hosts. Human macrophages are able to phagocytose and digest L. monocytogenes but IL-4 prevents human macrophages from killing the bacteria, the mechanisms of which are unknown.

[Totally artificial training model for coronary heart surgery: the renunciation of animal experiments?].

Aim: Animal protection laws will lead to stricter and more selective criteria thus resulting in a decline of available animals. Yet to train cardiac surgical skills a totally artificial training model was developed.

Description Of The Training Model: The model is based on differently hardened polyurethane.

Xenogeneic human NK cytotoxicity against porcine endothelial cells is perforin/granzyme B dependent and not inhibited by Bcl-2 overexpression.

Because of organ shortages in clinical allotransplantation, the potential of pig-to-human xenotransplantation is currently being explored showing a possible critical role for natural killer (NK) cells in the immune response against xenografts. Therefore, we analyzed the cytotoxic pathways utilized by human natural killer cells (hNK) against porcine endothelial cells (pEC). Transmission electron microscopy of pEC cocultured with hNK cells showed both apoptotic and necrotic cell death, whereas soluble factors such as Fas ligand or TNFalpha did not induce apoptosis in pEC.

Potassium-selective atomic force microscopy on ion-releasing substrates and living cells.

A new method for simultaneous mapping of cell topography and ion fluxes was developed. A highly sensitive ion sensor system was generated by coating atomic force microscopy tips with a PVC layer containing valinomycin, an ionophore for potassium. The activity of specific ions was traced on artificial ion-releasing PVC substrates.

Killing Mechanisms of Cytotoxic T Lymphocytes.

Cytotoxic T lymphocytes mediate lysis of target cells by various mechanisms, including exocytosis of lytic proteins (perforin, granzymes) and receptor-ligand binding of Fas/APO molecules. Death of target cells is characterized by either necrosis or apoptosis, depending on the killing mechanism used and on the metabolism of the target cell itself.