Publications (54) View all
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Article: Interactions of cnidarian toxins with the immune system.
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ABSTRACT: Cnidarians comprise four classes of toxic marine animals: Anthozoa, Cubozoa, Scyphozoa and Hydrozoa. They are the largest and probably the oldest phylum of toxic marine animals. Any contact with a cnidarian, especially the box jellyfish (Chironex fleckeri), can be fatal, but most cnidarians do not possess sufficiently strong venomous apparatus to penetrate the human skin, whereas others rarely come into contact with human beings. Only a small, almost negligible percentage of the vast wealth of cnidarian toxins has been studied in detail. Many polypeptide cnidarian toxins are immunogenic, and cross-reactivity between several jellyfish venoms has been reported. Cnidarians also possess components of innate immunity, and some of those components have been preserved in evolution. On the other hand, cnidarian toxins have already been used for the design of immunotoxins to treat cancer, whereas other cnidarian toxins can modulate the immune system in mammals, including man. This review will focus on a short overview of cnidarian toxins, on the innate immunity of cnidarians, and on the mode of action of cnidarian toxins which can modulate the immune system in mammals. Emphasis is palced on those toxins which block voltage activated potassium channels in the cells of the immune system.Inflammation & allergy drug targets. 10/2011; 10(5):429-37. -
Article: Segmentation priors from local image properties: without using bias field correction, location-based templates, or registration.
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ABSTRACT: We present a novel approach for generating information about a voxel's tissue class membership based on its signature--a collection of local image textures estimated over a range of neighborhood sizes. The approach produces a form of tissue class priors that can be used to initialize and regularize image segmentation. The signature-based approach is a departure from current location-based methods, which derive tissue class likelihoods based on a voxel's location in standard template space. To use location-based priors, one needs to register the volume in question to the template space, and estimate the image intensity bias field. Two optimizations, over more than a thousand parameters, are needed when high order nonlinear registration is employed. In contrast, the signature-based approach is independent of volume orientation, voxel position, and largely insensitive to bias fields. For these reasons, the approach does not require the use of population derived templates. The prior information is generated from variations in image texture statistics as a function of spatial scale, and an SVM approach is used to associate signatures with tissue types. With the signature-based approach, optimization is needed only during the training phase for the parameter estimation stages of the SVM hyperplanes, and associated PDFs; a training process separate from the segmentation step. We found that signature-based priors were superior to location-based ones aligned under favorable conditions, and that signature-based priors result in improved segmentation when replacing location-based ones in FAST (Zhang et al., 2001), a widely used segmentation program. The software implementation of this work is freely available as part of AFNI http://afni.nimh.nih.gov.NeuroImage 03/2011; 55(1):142-52. · 5.89 Impact Factor -
Article: Preapoptotic cell stress response of primary hepatocytes.
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ABSTRACT: Primary hepatocytes are an important in vitro model for studying metabolism in man. Caspase-9 and Bcl-2-associated X protein (Bax) are regulators of the apoptotic pathway. Here we report on the translocation of procaspase-9 and Bax from cytoplasm to nuclei as well as on dispersion of mitochondria; these processes occur after isolation of primary hepatocytes. The observed changes appear similar to those at the beginning of apoptosis; however, the isolated hepatocytes are not apoptotic for the following reasons: (1) cells have a normal morphology and function; (2) the mitochondria are energized; (3) there is no apoptosis unless it is induced by, e.g., staurosporine or nodularin. Staurosporine does not trigger apoptosis through activation of caspase-9, as its activity is detected later than that of caspase-3. We propose that the translocation of procaspase-9 and Bax into the nuclei reduces the ability to trigger apoptosis through the intrinsic apoptotic pathway. The shifts of procaspase-9 and Bax are reversible in the absence of the apoptotic trigger; the spontaneous reversion was confirmed experimentally for procaspase-9, whereas Bax shifted from the nuclei to the cytosol and mitochondria after the initiation of apoptosis. To distinguish this process from apoptosis, we call it preapoptotic cell stress response. It shares some features with apoptosis; however, it is reversible and apoptosis has to be induced in addition to this process. CONCLUSION: Knowledge on preapoptotic cell stress response is important for assessing the quality of the cells used in cell therapies, in regenerative medicine, and of those used for modeling metabolic processes.Hepatology 06/2010; 51(6):2140-51. · 11.66 Impact Factor -
Article: Parazoanthoxanthin A blocks Torpedo nicotinic acetylcholine receptors.
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ABSTRACT: Nicotinic acetylcholine receptors are implicated in different nervous system-related disorders, and their modulation could improve existing therapy of these diseases. Parazoanthoxanthin A (ParaA) is a fluorescent pigment of the group of zoanthoxanthins. Since it is a potent acetylcholinesterase inhibitor, it may also bind to nicotinic acetylcholine receptors (nAChRs). For this reason its effect on Torpedo nAChR (alpha1(2)betagammadelta) transplanted to Xenopus laevis oocytes was evaluated, using the voltage-clamp technique. ParaA dose-dependently reduced the acetylcholine-induced currents. This effect was fully reversible only at lower concentrations. ParaA also reduced the Hill coefficient and the time to peak current, indicating a channel blocking mode of action. On the other hand, the combined effect of ParaA and d-tubocurarine (d-TC) on acetylcholine-induced currents exhibited only partial additivity, assuming a competitive mode of action of ParaA on nAChR. These results indicate a dual mode of action of ParaA on the Torpedo AChR.Chemico-biological interactions 03/2010; 187(1-3):384-7. · 2.46 Impact Factor -
Article: Cardiotoxic injury caused by chronic administration of microcystin-YR.
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ABSTRACT: Microcystins are cyclic peptide toxins. Chronic intoxication with well-known members of the microcystin family--microcystins-LR--induces liver tumour formation, injury of kidney and heart. Despite worldwide distribution in the environment, the effects of microcystins-YR have not been studied extensively. The aim of the study was to evaluate whether microcystins-YR, in relatively low doses, have a toxic effect on cardiomyocytes of chronically treated rats. Male adult Wistar rats were treated every second day for 8 months with microcystins-YR (10 microg/kg i.p., N = 5). Control groups were treated either with vehicle (ethanol and methanol 4 : 1 v/v; N = 5) or with physiologic saline (N = 4). The heart sections of microcystin-YR-treated rats revealed decreased volume density of cardiac muscle tissue (microcystins- YR = 0.485 mm3/mm3 +/- 0.003; vehicle = 0.493 mm3/mm3 +/- 0.002; saline = 0.492 mm3/mm3 +/- 0.002) due to fibrous proliferation. A few lymphocyte infiltrates were observed. Most of cardiomyocytes were enlarged (microcystins-YR = 20.19 microm +/- 1.34, vehicle = 17.45 microm +/- 0.52, saline = 16.00 microm +/- 1.43), with enlarged and often bizarre-shaped nuclei and decreased myofibril volume fraction (microcystins- YR = 0.416 mm3/mm3 +/- 0.009; vehicle = 0.472 mm3/ mm3 +/- 0.009; saline = 0.479 mm3/mm3 +/- 0.010). No TUNEL-positive cells were found in the heart sections of rats in all groups. The results allow the conclusion that chronic exposure to low doses of microcystins-YR may cause atrophy and fibrosis of the heart muscle.Folia biologica 01/2010; 56(1):14-8. · 1.15 Impact Factor
