This article reviews the role of the signal transduction enzyme protein kinase C in the regulation of growth of malignant gliomas, and describes how targetting this enzyme clinically can provide a ...novel approach to glioma therapy.
Objective
To investigate expression of the chemokine receptor CCR2 on key cell types involved in the pathogenesis of systemic sclerosis (SSc) and to assess the potential for autocrine activation of ...SSc dermal fibroblasts via CCL2/CCR2.
Methods
Chemokine receptor expression in skin biopsy tissues and explanted dermal fibroblasts from a well‐characterized cohort of SSc patients was examined using immunohistochemistry and flow cytometry techniques. Autocrine regulation of the expression of fibrotic markers in CCR2+ SSc fibroblast cell lines was assessed using specific ligand or receptor antagonists.
Results
We identified strong CCR2 expression in skin biopsy samples of early‐stage diffuse cutaneous SSc (dcSSc), but not late‐stage dcSSc or limited cutaneous SSc. Double labeling confirmed up‐regulation of CCL2/CCR2 on myofibroblasts, pericytes, lymphocytes, macrophages, and endothelial cells. Explanted dermal fibroblasts from early dcSSc tissues expressed CCR2 and CXCR2 in 55% and 66% of cell strains, respectively. There was no expression in control fibroblasts. CCR2+ fibroblasts demonstrated a profibrotic phenotype, with overexpression of α‐smooth muscle actin (α‐SMA), connective tissue growth factor (CTGF), and CCL2. Flow cytometric analysis identified a subset of CCR2+ SSc fibroblasts expressing the myofibroblast marker α‐SMA. In these cultures, specific inhibition of CCL2 or CCR2 attenuated the overexpression of α‐SMA, but not CTGF or plasminogen activator inhibitor 1.
Conclusion
Our results show that CCR2 is up‐regulated in early dcSSc on cell types known to be activated in the disease, which is consistent with a key role in SSc pathogenesis. CCR2 expression on SSc fibroblasts appears to regulate the expression of CCL2 and α‐SMA. Our findings suggest potential autocrine regulation of key profibrotic properties via a CCL2/CCR2 loop in early‐stage dcSSc.
Objective
To determine the gene‐expression profile in dermal fibroblasts from type 1 tight‐skin (Tsk1) mice, and to examine the expression and potential fibrotic activity of monocyte chemoattractant ...protein 3 (MCP‐3) in Tsk1 mouse and human systemic sclerosis (SSc) skin.
Methods
Complementary DNA microarrays (Atlas 1.2) were used to compare Tsk1 fibroblasts with non‐Tsk1 littermate cells at 10 days, 6 weeks, and 12 weeks of age. Expression of MCP‐3 protein was assessed by Western blotting of fibroblast culture supernatants, and localized in the mouse and human skin biopsy samples by immunohistochemistry. Activation of collagen reporter genes by MCP‐3 was explored in transgenic mouse fibroblasts and by transient transfection assays.
Results
MCP‐3 was highly overexpressed by neonatal Tsk1 fibroblasts and by fibroblasts cultured from the lesional skin of patients with early‐stage diffuse cutaneous SSc. Immunolocalization confirmed increased expression of MCP‐3 in the dermis of 4 of 5 Tsk1 skin samples and 14 of 28 lesional SSc skin samples, compared with that in matched healthy mice (n = 5) and human controls (n = 11). Proα2(I) collagen promoter–reporter gene constructs were activated by MCP‐3 in transgenic mice and by transient transfection assays. This response was maximal between 16 and 24 hours of culture and mediated via sequences within the proximal promoter. The effects of MCP‐3 could be diminished by a neutralizing antibody to transforming growth factor β.
Conclusion
We demonstrate, for the first time, overexpression of MCP‐3 in early‐stage SSc and in Tsk1 skin, and suggest a novel role for this protein as a fibrotic mediator activating extracellular matrix gene expression in addition to promoting leukocyte trafficking. This chemokine may be an important early member of the cytokine cascade driving the pathogenesis of SSc.
Vision-based automated parking system Al-Absi, H R H; Devaraj, J D D; Sebastian, P ...
10th International Conference on Information Science, Signal Processing and their Applications (ISSPA 2010)
Conference Proceeding
This paper describes an approach to overcome a situation of monitoring and managing a parking area using a vision based automated parking system. With the rapid increase of cars the need to find ...available parking space in the most efficient manner, to avoid traffic congestion in a parking area, is becoming a necessity in car park management. Current car park management is dependent on either human personnel keeping track of the available car park spaces or a sensor based system that monitors the availability of each car park space or the overall number of available car park spaces. In both situations, the information available was only the total number of car park spaces available and not the actual location available. In addition, the installation and maintenance cost of a sensor based system is dependent on the number of sensors used in a car park. This paper shows a vision based system that is able to detect and indicate the available parking spaces in a car park. The methods utilized to detect available car park spaces were based on coordinates to indicate the regions of interest and a car classifier. This paper shows that the initial work done here has an accuracy that ranges from 90% to 100% for a 4 space car park. The work done indicated that the application of a vision based car park management system would be able to detect and indicate the available car park spaces.
Laser profilometry offers new possibilities to improve non-invasive tumor diagnostics in dermatology. In this paper, a new approach to computer-supported analysis and interpretation of ...high-resolution skin-surface profiles of melanomas and nevocellular nevi is presented. Image analysis methods are used to describe the profile's structures by texture parameters based on co-occurrence matrices, features extracted from the Fourier power spectrum, and fractal features. Different feature selection strategies, including genetic algorithms, are applied to determine the best possible subsets of features for the classification task. Several architectures of multilayer perceptrons with error back-propagation as learning paradigm are trained for the automatic recognition of melanomas and nevi. Furthermore, network-pruning algorithms are applied to optimize the network topology. In the study, the best neural classifier showed an error rate of 4.5% and was obtained after network pruning. The smallest error rate in all, of 2.3%, was achieved with nearest neighbor classification.
Surgical fluid replacement is a critical issue in medicine as the fluid volume excess or deficit can both complicate the patient's condition. Currently, the administration of fluid volume is carried ...out primarily based on the experience and expertise of the anaesthetist as there is no analytical method available to estimate the patient's fluid level. The development of a decision support system (DSS) to assist the anaesthetist in estimating the required fluid infusion rate for a particular patient has been the focus of this research paper. The DSS is developed based on Fuzzy Logic Control (FLC) technique which is ideal for developing input/output models in an unstructured and/or complex environment. The fuzzy rules used in the DSS are derived automatically from the clinical data produced in surgical operations. The DSS employs a Multi Rule Base (MRB) learning scheme to adapt its model according to the significant variation in the physiological parameters of a patient. The performance of the developed algorithms is validated through experimental work using clinical data. The results obtained so far are encouraging.
Analysis of the response of baby hamster kidney cells to adenosine in the presence of the adenosine deaminase inhibitor erythro-9-(2-hydroxy-3-nonyl) adenine has revealed two distinct mechanisms of ...toxicity. The first is apparent at low concentrations of adenosine (less than 5 microM) and is dependent upon the presence of a functional adenosine kinase. The initial toxicity is abolished by uridine, is unrelated to the inhibition of ribonucleotide reductase, and is accompanied by a decrease in the size of the pyrimidine nucleotide pool. Toxicity at higher concentrations of adenosine is adenosine kinase independent and is potentiated by homocysteine thiolactone. An elevation in the intracellular level of S-adenosylhomocysteine, which was observed following treatment with higher concentrations of adenosine (greater than 10 microM), is believed to mediate toxicity at these levels. Interestingly, BHK cells were resistant to intermediate levels of adenosine. The mechanism of resistance is currently unknown, but appears unrelated to a lack of inhibition of adenosine deaminase. It is proposed that substrate inhibition of adenosine kinase may be a determinant of this property.
Human DNA was used to transform adenosine kinase (AK)-deficient BHK cells followed by selection of AK+ cells in medium containing alanosine, adenosine, and uridine (AAU medium). Twenty AAUr isolates ...were analyzed, and none of them contained AK activity. Several purine salvage enzymes were, however, found to be affected in these cells. The levels of hypoxanthine-guanine phosphoribosyltransferase and adenylosuccinate synthetase activities were elevated, while the adenylosuccinase activity was reduced. AAU-resistance may be explained by elevated activity of adenylosuccinate synthetase to overcome the alanosine block; thus AAUr cells were able to convert exogenous adenosine---inosine---hypoxanthine---IMP---AMPS---AMP. Moreover, these AAUr cells required exogenous purines for growth. HPLC analyses of endogenous nucleotide pools of AAUr cells showed that the levels of adenine nucleotides have diminished to less than 10% of the parental levels. These results suggest that the AAU-resistant mutation, which elicits pleiotropic phenotypes in BHK cells, affects an important component in the regulation of adenine nucleotide synthesis. By including erthyro-9-(2-hydroxy-3-nonyl)adenine in the AAU medium (renamed as AAUE medium) to block deamination of adenosine, AK+ BHK cells were isolated.
A 76-year-old woman was admitted due to recurrent syncope. Sinus bradycardia and intermittent sinus pauses (up to 2.24 sec) were documented by 24 hour Holter electrocardiogram. Although intravenous ...atropine can increase the sinus rate up to 100 bpm, electrophysiologic study showed marked prolongation of sinus node recovery time both at the control state and after autonomic blockades. Sick sinus syndrome was diagnosed, even with a normal atropine test, and a permanent pacemaker resulted in resolution of the syncope.
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