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Selected Abstractsica and beyond: biofilm mechanisms and regulation in Staphylococcus epidermidis and Staphylococcus aureusFEMS MICROBIOLOGY LETTERS, Issue 2 2007James P. O'Gara Abstract Recent progress in elucidating the role of the icaADBC -encoded polysaccharide intercellular adhesin (PIA) or polymeric N -acetyl-glucosamine (PNAG) in staphylococcal biofilm development has in turn contributed significantly to our understanding of the pathogenesis of device-related infections. Nevertheless, our understanding of how the ica locus and PIA/PNAG biosynthesis are regulated is far from complete and many questions remain. Moreover, beyond ica, evidence is now emerging for the existence of ica -independent biofilm mechanisms in both Staphylococcus aureus and Staphylococcus epidermidis. Teichoic acids, which are a major carbohydrate component of the S. epidermidis biofilm matrix and the major cell wall autolysin, play an important role in the primary attachment phase of biofilm development, whereas the cell surface biofilm-associated protein and accumulation-associated protein are capable of mediating intercellular accumulation. These findings raise the exciting prospect that other surface proteins, which typically function as antigenic determinants or in binding to extracellular matrix proteins, may also act as biofilm adhesins. Given the impressive array of surface proteins expressed by S. aureus and S. epidermidis, future research into their potential role in biofilm development either independent of PIA/PNAG or in cooperation with PIA/PNAG will be of particular interest. [source] Stem cell-based cell therapy for Huntington disease: A reviewNEUROPATHOLOGY, Issue 1 2008Manho Kim Huntington disease (HD) is a devastating neurodegenerative disorder and no proven medical therapy is currently available to mitigate its clinical manifestations. Although fetal neural transplantation has been tried in both preclinical and clinical investigations, the efficacy is not satisfactory. With the recent explosive progress of stem cell biology, application of stem cell-based therapy in HD is an exciting prospect. Three kinds of stem cells, embryonic stem cells, bone marrow mesenchymal stem cells and neural stem cells, have previously been utilized in cell therapy in animal models of neurological disorders. However, neural stem cells were preferably used by investigators in experimental HD studies, since they have a clear capacity to become neurons or glial cells after intracerebral or intravenous transplantation, and they induce functional recovery. In this review, we summarize the current state of cell therapy utilizing stem cells in experimental HD animal models, and discuss the future considerations for developing new therapeutic strategies using neural stem cells. [source] Mechanisms of lymphatic metastasis in human colorectal adenocarcinoma,THE JOURNAL OF PATHOLOGY, Issue 5 2009Daniel Royston Abstract The invasion of lymphatic vessels by colorectal cancer (CRC) and its subsequent spread to draining lymph nodes is a key determinant of prognosis in this common and frequently fatal malignancy. Although tumoural lymphangiogenesis is assumed to contribute to this process, review of the current literature fails to support any notion of a simple correlation between lymphatic vessel density and CRC metastasis. Furthermore, attempts to correlate the expression of various lymphangiogenic growth factors, most notably VEGF-C and VEGF-D, with the lymphatic metastasis of CRC have provided contradictory results. Recent evidence from animal and human models of tumour metastasis suggests that complex functional and biochemical interactions between the microvasculature of tumours and other cell types within the tumour microenvironment may play a pivotal role in the behaviour of commonly metastasizing tumours. Indeed, previous insights into tumoural blood vessels have provided candidate markers of tumoural angiogenesis that are currently the subject of intense investigation as future therapeutic targets. In this review article we survey the current evidence relating lymphangiogenesis and lymphangiogenic growth factor production to metastasis by CRC, and attempt to provide some insight into the apparent discrepancies within the literature. In particular, we also discuss some new and provocative insights into the properties of tumoural lymphatics suggesting that they have specific expression profiles distinct from those of normal lymphatic vessels and that appear to promote metastasis. These findings raise the exciting prospect of future biomarkers of lymphatic metastasis and identify potential targets for new generation anti-tumour therapies. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] Vascular Mimicry of Granulosa Cells: a New Concept of Corpeus Luteum Development?ANATOMIA, HISTOLOGIA, EMBRYOLOGIA, Issue 2005R. M. Hirschberg So far, it was generally accepted that newly formed blood vessels are exclusively comprised of endothelial cells, and complemented by pericyte and myocyte recruitment during vessel maturation. Accordingly, participation of non-endothelial cells in the formation of blood vessels has rarely been suggested. Recently, evidence supporting the existence of tumour vessels lined by non-endothelial cells has emerged. Consequently, the concept of the inherent capacity of non-endothelial cells to behave like endothelial cells has been discussed for tumours, and this pathomechanism has been termed vascular mimicry. The corpus luteum is one of the most intensely vascularized tissues, and angiogenesis in the corpus luteum is more effective than in highly malignant tumours. Our results indicate active involvement of granulosa cells in luteal angiogenesis, and the aim of this study was to shed more light on this exciting prospect. The study was based on cultured granulosa cells isolated from the bovine ovary in different stages of follicle maturation. Morphology of angiogenic granulosa cells was studied by phase contrast, transmission electron and scanning electron microscopy. Expression of angiogenesis-regulating factors and their receptors was demonstrated by polymerase chain reaction (RT-PCR). Cultured granulosa cells underwent changes reminiscent of endothelial angiogenesis, i.e., migration, proliferation, differentiation and three-dimensional organization, and expressed angiogenesis-regulating factors and their receptors. Our results suggest a tight regulatory and structural association of endothelial and granulosa cells in luteal angiogenesis, suggesting physiological vascular mimicry in the ovary. [source] Tamoxifen (ICI46,474) as a targeted therapy to treat and prevent breast cancerBRITISH JOURNAL OF PHARMACOLOGY, Issue S1 2006V Craig Jordan Antihormonal therapy targeted to the oestrogen receptor (OER) is recognized as a significant advance in the treatment and prevention of breast cancer. However, the research method used to achieve the current successes seen in the clinic was not linear but was based on the changing fashions in research and the application of appropriate testing models. The discovery and investigation of nonsteroidal antioestrogens by the pharmaceutical industry during the 1960s was initially an exciting prospect for clinical development. The drugs were superb antifertility agents in laboratory animals, so the prospect of marketing a ,morning after' pill was a high priority. Unfortunately, the reproductive endocrinology of the rat was found to be completely different from that of the human. Antioestrogens, in fact, improved fertility by inducing ovulation in subfertile women so much of the drug development was discontinued. The successful reinvention of ICI46,474 from its origins as a failed contraceptive to a pioneering breast cancer treatment targeted to the OER presaged the development of the current menu of medicines targeted to a range of different survival mechanisms in cancer cells. British Journal of Pharmacology (2006) 147, S269,S276. doi:10.1038/sj.bjp.0706399 [source] Lung Function Tests in Neonates and Infants with Chronic Lung Disease: Global and Regional Ventilation InhomogeneityPEDIATRIC PULMONOLOGY, Issue 2 2006J. Jane Pillow FRACP Abstract This review considers measurement of global and regional ventilation inhomogeneity (VI) in infants and young children with acute neonatal respiratory disorders and chronic lung disease of infancy (CLDI). We focus primarily on multiple-breath inert gas washout (MBW) and electrical impedance tomography (EIT). The literature is critically reviewed and the relevant methods, equipment, and studies are summarized, including the limitations and strengths of individual techniques, together with the availability and appropriateness of any reference data. There has been a recent resurgence of interest in using MBW to monitor lung function within individuals and between different groups. In the mechanically ventilated, sedated, and paralyzed patient, VI indices can identify serial changes occurring following exogenous surfactant. Similarly, global VI indices appear to be increased in infants with CLDI and to differentiate between infants without lung disease and those with mild, moderate, and severe lung disease following preterm birth. While EIT is a relatively new technique, recent studies suggest that it is feasible in newborn infants, and can quantitatively identify changes in regional lung ventilation following alterations to ventilator settings, positive end expiratory pressure (PEEP), and administration of treatments such as surfactant. As such, EIT represents one of the more exciting prospects for continuous bedside pulmonary monitoring. For both techniques, there is an urgent need to establish guidelines regarding data collection, analysis, and interpretation in infants both with and without CLDI. © 2005 Wiley-Liss, Inc. [source] Quantitative Reflection Interference Contrast Microscopy (RICM) in Soft Matter and Cell AdhesionCHEMPHYSCHEM, Issue 16 2009Laurent Limozin Dr. Abstract Adhesion can be quantified by measuring the distance between the interacting surfaces. Reflection interference contrast microscopy (RICM), with its ability to measure inter-surface distances under water with nanometric precision and milliseconds time resolution, is ideally suited to studying the dynamics of adhesion in soft systems. Recent technical developments, which include innovative image analysis and the use of multi-coloured illumination, have led to renewed interest in this technique. Unambiguous quantitative measurements have been achieved for colloidal beads and model membranes, thus revealing new insights and applications. Quantification of data from cells shows exciting prospects. Herein, we review the basic principles and recent developments of RICM applied to studies of dynamical adhesion processes in soft matter and cell biology and provide practical hints to potential users. [source] |