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Global Effect (global + effect)

Distribution by Scientific Domains
Medical Sciences71%

Selected Abstracts

Molecular characterization of the effects of Y-27632

CYTOSKELETON, Issue 2 2007
Hassina Darenfed
Abstract Many key cellular functions, such as cell motility and cellular differentiation are mediated by Rho-associated protein kinases (ROCKs). Numerous studies have been conducted to examine the ROCK signal transduction pathways involved in these motile and contractile events with the aid of pharmacological inhibitors such as Y-27632. However the molecular mechanism of action of Y-27632 has not been fully defined. To assess the relative contribution of these Rho effectors to the effects of Y-27632, we compared the cytoskeletal phenotype, wound healing and neurite outgrowth in cells treated with Y-27632 or subjected to knockdown with ROCK-I, ROCK-II or PRK-2- specific siRNAs. Reduction of ROCK-I enhances the formation of thin actin-rich membrane extensions, a phenotype that closely resembles the effect of Y-27632. Knockdown of ROCK II or PRK-2, leads to the formation of disc-like extenstions and thick actin bundles, respectively. The effect of ROCK-I knockdown also mimicked the effect of Y-27632 on wound closer rates. ROCK-I knockdown and Y-27632 enhanced wound closure rates, while ROCK-II and PRK-2 were not appreciably different from control cells. In neurite outgrowth assays, knockdown of ROCK-I, ROCK-II or PRK-2 enhances neurite lengths, however no individual knockdown stimulated neurite outgrowth as robustly as Y-27632. We conclude that several kinases contribute to the global effect of Y-27632 on cellular responses. Cell Motil. Cytoskeleton 2006. © 2006 Wiley-Liss, Inc. [source]

Validation of a New Noninvasive Device for the Monitoring of Peak Endocardial Acceleration in Pigs: Implications for Optimization of Pacing Site and Configuration

JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 7 2008
PIERRE BORDACHAR M.D.
Introduction: The peak of endocardial acceleration (PEA) is an index of myocardial contractility. We aimed to (1) demonstrate that the PEA measured by the noninvasive cutaneous precordial application of an accelerometer sensor is related to left ventricular (LV) dP/dt max and (2) assess the usefulness of PEA monitoring during graded ischemia and during different configurations of sequential biventricular pacing. Methods and Results: Measurements of invasive LV dP/dt max were compared with measurements of transcutaneous PEA in seven pigs at baseline and during acute drug infusions; increased heart rate; right, left, biventricular and sequential biventricular pacing before and after graded ischemia induced by the constriction of the left anterior descending coronary artery. A consistent PEA signal was obtained in all animals. PEA changes were highly related to LV dP/dt max changes (r= 0.93; P < 0.001). The changes of LV contractility induced by the different pacing configurations were detected by PEA analysis in the absence of ischemia (r= 0.94; P < 0.001) and in the presence of ischemic LV dysfunction (r= 0.91; P < 0.001). Conclusion: Noninvasive PEA measurement allows monitoring of left ventricular contractility and may be a useful tool to detect global effect of ventricular ischemia and to optimize the choice of both pacing site and pacing configuration. [source]

Vasopressin Preferentially Depresses Excitatory Over Inhibitory Synaptic Transmission in the Rat Supraoptic Nucleus In Vitro

JOURNAL OF NEUROENDOCRINOLOGY, Issue 4 2000
Kombian1
Endogenous arginine-vasopressin (AVP) in the supraoptic nucleus is known to decrease the firing rate of some supraoptic nucleus neurones. To determine a possible mechanism by which this locally released AVP produces this change in neuronal excitability, we investigated the effects of AVP on evoked excitatory (e.p.s.c.) and inhibitory post-synaptic (i.p.s.c.) responses recorded in magnocellular neurones in a hypothalamic slice preparation, using the perforated-patch recording technique. Our data show that AVP produces a dose-dependent decrease in the evoked e.p.s.c. in about 80% of magnocellular neurones tested with an estimated EC50 of about 0.9 ,M. The maximum decrease in e.p.s.c. amplitude was about 31% of control and was obtained with an AVP concentration of 2 ,M. The AVP-induced synaptic depression was blocked by Manning Compound (MC), a non-selective antagonist of oxytocin (OXT) and vasopressin (AVP) receptors, but not by a selective OXT receptor antagonist. It was not mimicked by desmopressin (ddAVP), a V2-receptor subtype agonist. By contrast, AVP used at the same concentration (2 ,M), had no global effect on pharmacologically isolated i.p.s.c.s in the majority of magnocellular neurones tested. These results show that AVP acts in the supraoptic nucleus to reduce excitatory synaptic transmission to magnocellular neurones by activating a non-OXT receptor, presumably the V1 receptor subtype. [source]

The mechanisms of tumor suppressor effect of glucocorticoid receptor in skin

MOLECULAR CARCINOGENESIS, Issue 8 2007
Dmitry Chebotaev
Abstract Glucocorticoid hormones exert a tumor suppressor effect in different experimental models, including mouse skin carcinogenesis. The glucocorticoid control of cellular functions is mediated via the glucocorticoid receptor (GR), a well-known transcription factor that regulates genes by DNA-binding dependent transactivation, and DNA-binding independent transrepression through negative interaction with other transcription factors. In this perspective, we analyze known mechanisms that underlie the anticancer effect of GR signaling, including effects on cell growth, differentiation, apoptosis, and angiogenesis. We also discuss a novel mechanism for the tumor suppressor effect of the GR in skin: through the regulation of the number and status of follicular epithelial stem cells (SC), which are a target cell population for skin carcinogenesis. Our studies on keratin5.GR transgenic animals that are resistant to skin carcinogenesis, demonstrated that the GR diminishes the number of follicular epithelial SCs, reduces their proliferative and survival potential and affects the expression of follicular SC "signature" genes. The analysis of global effect of the GR on gene expression in follicular epithelial SCs, basal keratinocytes, and mouse skin tumors provided an unexpected evidence that gene transrepression by GR plays an important role in the maintenance of SC and in inhibition of skin carcinogenesis by this steroid hormone receptor. It is known that antiinflammatory effect of glucocorticoids is chiefly mediated by GR transrepression. Thus, our findings suggest the similarity between the mechanisms of antiinflammatory and anticancer effects of the GR signaling. We discuss the potential clinical applications of our findings in light of drug discovery programs focused on the development of selective GR modulators that preferentially induce GR transrepression. © 2007 Wiley-Liss, Inc. [source]

k-space analysis of point-resolved spectroscopy (PRESS) with regard to spurious echoes in in vivo1H MRS

NMR IN BIOMEDICINE, Issue 2 2009
G. Starck
Abstract The spurious echo artefact, not uncommon in 1H MRS in the brain, comes from refocusing outer volume signal. Application of MRS in small volumes in susceptibility-affected regions often results in large shim gradients. The artefact problem is accentuated when the global effect of the shim gradient shifts the water resonance outside the water suppression band in the outer volume. This scenario brings the issue of spurious echoes once again to the fore. In this paper, spurious signals of the point-resolved spectroscopy (PRESS) sequence are analysed using the concept of k-space. This new approach facilitates a more geometrical view of the problem, well suited for studying the effect of gradient spoiling and refocusing of signal. Several spoiling options are shown, and the probability of the global effects of shimming being a primary cause of the artefact is discussed. Fourier transform analysis of realistic slice profiles, combined with the k-space description of spurious echoes, shows that unsuppressed water signal in outer regions greatly increases the demands on spoiling. Gradient spoiling adequate for artefact suppression at a given size of MRS volume may not be sufficient at a smaller size. Several ways to improve PRESS measurements with regard to suppression of spurious signal are discussed. Copyright © 2008 John Wiley & Sons, Ltd. [source]

Protein chip-based microarray profiling of oxidized low density lipoprotein-treated cells

PROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 5 2005
Sergiy Sukhanov
Abstract Commercially available high-content Ab380 and extensively validated DLM26 homemade protein microarrays were used to profile the effects of the pro-atherogenic molecule, oxidized low density lipoprotein (OxLDL), on human aortic smooth muscle cells. Protein microarrays detected 298 proteins in cell lysates and 54 of these were differentially regulated. Microarray data were validated by immunoblotting for a selected set of up- and down-regulated proteins. The protein microarray data sets were compared with our recent cDNA microarray-based gene expression results in order to characterize the global effect of OxLDL on smooth muscle cell functions. A group of cell-cell interaction molecules was classified as up-regulated by OxLDL, whereas nucleic acid/protein biosynthesis, structural and humoral response proteins/genes were under-expressed in cells treated by OxLDL. These findings reveal the major pattern of OxLDL-induced effects on the human aortic smooth muscle cells functions and also demonstrate that protein chip-based microarrays could be a useful proteomic tool to profile disease-related states of muscle cells. [source]

The Role of Angiogenic and Wound Repair Factors During CMV-Accelerated Transplant Vascular Sclerosis in Rat Cardiac Transplants

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 2 2008
D. N. Streblow
Human cytomegalovirus (HCMV) accelerates transplant vascular sclerosis (TVS), a consequence of angiogenesis (AG) and wound repair (WR). While HCMV can be localized to TVS lesions, the low number of infected cells suggests a global effect on target tissues. We used microarray analysis followed by real-time-polymerase chain reaction (RT-PCR) in an RCMV-accelerated TVS rat cardiac transplant model to determine whether CMV activates host WR and AG factors. Dysregulated cellular genes in allografts from RCMV-infected recipients were compared to those from uninfected recipients and native hearts. We demonstrated that RCMV upregulates the genes involved in WR and AG, which was highest during the critical time of TVS acceleration (21,28 days). Using a standard in vitro AG assay, virus and serum-free supernatants collected at 48 h postinfection significantly induced endothelial cell (EC) migration, branching and tubule formation compared to supernatants from mock-infected cells. Supernatants from ultraviolet (UV)-inactivated RCMV-infected cells failed to induce AG, indicating that virus replication is required. Upregulation of WR and AG genes occurs during the critical period of CMV-accelerated TVS. Targeting these genes may prevent this process and improve allograft survival. [source]