Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Rage”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 163 records · Page 9Linked to original sources
PubMed1994

Basal amygdaloid facilitation of midbrain periaqueductal gray elicited defensive rage behavior in the cat is mediated through NMDA receptors.

The present study tested the hypotheses that: (1) defensive rage behavior elicited from the midbrain periaqueductal gray (PAG) in the cat is facilitated from the basal complex of amygdala; and (2) such facilitation from this region of amygdala is mediated via a pathway in which excitatory amino acids acting upon NMDA receptors within the PAG are utilized as a neurotransmitter. In the first phase of this study, cannula electrodes were implanted into PAG sites for the elicitation of defensive rage behavior as well as for drug delivery. Then, a second monopolar electrode was implanted into the basal nucleus of amygdala from which facilitation of defensive rage could be obtained. As a result of dual stimulation of the basal amygdala and PAG, response latencies for defensive rage were significantly lowered relative to PAG stimulation alone (P < 0.01). In the second phase of this experiment, 3 doses of a selective NMDA receptor antagonist, AP-7 (0.1, 0.5, 1.0 mg/kg), were peripherally (i.p.) administered in 5 animals. The results indicated a significant decrease in the facilitatory effects of amygdaloid stimulation in a dose and time dependent manner (P < 0.001). In the third phase, AP-7 was administered intracerebrally into PAG defensive rage sites in doses of 0.2 and 2.0 nmol. It was noted that intracerebral microinjections of AP-7 at the higher dose (2.0 nmol) also significantly suppressed the facilitatory effects of amygdaloid stimulation (P < 0.01); however, these effects were somewhat less potent then those observed following peripheral drug administration. A fourth phase of the study was conducted at the completion of the pharmacological experiments.(ABSTRACT TRUNCATED AT 250 WORDS)

2-Amino-5-phosphonovalerate↗
PubMed2006

Can we prevent road rage?

Road rage has become a serious concern in many countries, and preventive efforts are required. This article reviews what can be done to prevent road rage by exploring potential prevention avenues in five areas. First, legal changes aimed at increasing the penalties for road rage behavior could be instituted, drawing on models from aggressive-driving or impaired-driving laws. A second approach would involve the adoption of court programs for convicted road ragers. Third, car redesign offers a means of reducing crime through environmental design. Fourth, mass media education could be implemented to inform drivers of the risk from road rage and how to avoid situations that facilitate road rage. Finally, prevention efforts could be directed to long-term societal changes that emphasize structural modifications, such as reducing congestion on the roads, reduced driver stress, or promoting public transportation. The strengths and weaknesses of these strategies are discussed.

Accidents, Traffic↗
PubMed1998

Rage attacks in children and adolescents with Tourette's disorder: a pilot study.

BACKGROUND: Sudden, explosive episodes of rage occur in a significant number of clinically referred children with Tourette's disorder and cause considerable psychosocial morbidity. The etiology of these symptoms is unknown. We conducted a pilot study of 12 consecutive children with Tourette's disorder and rage attacks to determine whether comorbidity of Tourette's-associated disorders is related to these symptoms. METHOD: Twelve consecutive children with Tourette's disorder who presented with rage attacks were evaluated, including 2 females and 10 males. Tourette's disorder diagnosis, presence of comorbid disorders, and tic severity were assessed using DSM-IV diagnostic criteria and standardized rating scales. RESULTS: All 12 children met diagnostic criteria for Tourette's disorder, obsessive-compulsive disorder (OCD), and attention-deficit/hyperactivity disorder (ADHD). Two children were also diagnosed with comorbid oppositional defiant disorder, and 4 children were diagnosed with comorbid conduct disorder. None of the subjects met diagnostic criteria for a mood disorder. All subjects had only mild tic severity. CONCLUSION: The clinical phenomenon of rage attacks in children with Tourette's disorder resembles intermittent explosive disorder and may reflect specific underlying neurologic disturbances. This pilot study suggests that rage attacks in Tourette's disorder may be related to the presence of comorbid disorders.

Adolescent↗
PubMed2004

Blockade of receptor for advanced glycation end product (RAGE) attenuates ischemia and reperfusion injury to the liver in mice.

Hepatic ischemia/reperfusion (I/R) injury associated with liver transplantation and hepatic resection is characterized by hepatocellular damage and a deleterious inflammatory response. In this study, we examined whether receptor for advanced glycation end product (RAGE) activation is linked to mechanisms accentuating inflammation on I/R in a murine model of total hepatic ischemia. Animals treated with soluble RAGE (sRAGE), the extracellular ligand-binding domain of RAGE, displayed increased survival after total hepatic I/R compared with vehicle treatment. TUNEL assay and histologic analysis revealed that blockade of RAGE was highly protective against hepatocellular death and necrosis on I/R; in parallel, proliferating cell nuclear antigen was enhanced in livers of mice treated with sRAGE. Rapid activation of p38, p44/42, stress-activated protein kinase and c-Jun N-terminal kinase mitogen-activated protein kinases, signal transducer and activator of transcription-3, and nuclear translocation of activator protein-1 was evident at early times on I/R. In the remnants of sRAGE-treated livers, however, activation of each of these signaling and transcription factor pathways was strikingly decreased. sRAGE-treated remnants displayed enhanced activation of nuclear factor kappaB, in parallel with increased transcripts for the proregenerative cytokine, tumor necrosis factor-alpha. In conclusion, these data suggest that RAGE modulates hepatic I/R injury, at least in part by activation of key signaling pathways linked to proinflammatory and cell death-promoting responses. We propose that blockade of this pathway may represent a novel strategy to attenuate injury in hepatic I/R and to facilitate regeneration.

Animals↗
PubMed2006

S100B protects LAN-5 neuroblastoma cells against Abeta amyloid-induced neurotoxicity via RAGE engagement at low doses but increases Abeta amyloid neurotoxicity at high doses.

At the concentrations normally found in the brain extracellular space the glial-derived protein, S100B, protects neurons against neurotoxic agents by interacting with the receptor for advanced glycation end products (RAGE). It is known that at relatively high concentrations S100B is neurotoxic causing neuronal death via excessive stimulation of RAGE. S100B is detected within senile plaques in Alzheimer's disease, where its role is unknown. The present study was undertaken to evaluate a putative neuroprotective role of S100B against Abeta amyloid-induced neurotoxicity. We treated LAN-5 neuroblastoma cultures with toxic amounts of Abeta25-35 amyloid peptide. Our results show that at nanomolar concentrations S100B protects cells against Abeta-mediated cytotoxicity, as assessed by 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and terminal deoxynucleotidyl transferase-mediated dUTP-fluorescein isothiocyanate nick end-labeling (TUNEL) experiments, by countering the Abeta-mediated decrease in the expression of the anti-apoptotic factor Bcl-2. This effect depends on S100B binding to RAGE because S100B is unable to contrast Abeta-mediated neurotoxicity in neurons overexpressing a signaling-deficient RAGE mutant lacking the cytosolic and transducing domain. Our data suggest that at nanomolar doses S100B counteracts Abeta peptide neurotoxicity in a RAGE-mediated manner. However, at micromolar doses S100B is toxic to LAN-5 cells and its toxicity adds to that of the Abeta peptide, suggesting that additional molecular mechanisms may be involved in the neurotoxic process.

Amyloid beta-Peptides↗
PubMed1996

A T1-weighted rapid three-dimensional gradient-echo technique (MP-RAGE) in preoperative MRI of intracranial tumours.

Our purpose was to determine the value of a T1-weighted rapid three-dimensional gradient-echo technique in preoperative MRI of brain tumours. We examined 30 patients with intracranial tumours who underwent neurosurgery, using T1-weighted magnetisation-prepared rapid gradient-echo (MP-RAGE) and axial T1-weighted spin-echo (SE) sequences, both before and after contrast medium (Gd-DTPA). Signal and contrast behaviour of anatomical and pathological structures were assessed with regions-of-interest (ROI) and visual inspection. Imaging results were compared with operative results. In 5 cases tumours and anatomical structures were segmented in MP-RAGE data sets. The MP-RAGE sequence considerably improved delineation of grey and white matter and small anatomical structures (vessels, cranial nerves), and significantly reduced flow artefacts. Contrast behaviour of tumours was similar with both techniques. Correlation of imaging with the operative results confirmed the reliability of the MP-RAGE sequence. Segmentation of MP-RAGE data sets allows three-dimensional display, which enables one to document the relevant information on a few images in selected cases.

Adolescent↗
PubMed1991

Magnetization prepared rapid gradient-echo (MP-RAGE) MR imaging of the liver: comparison with spin-echo imaging.

We have implemented an MR technique that employs a rapid gradient echo sequence, preceded by magnetization preparation pulses to provide T1- and T2-weighted tissue contrast. With this technique, which can be identified as a member of a new family of pulse sequences, generically named Magnetization Prepared RApid Gradient Echo (MP-RAGE), very short repetition times are used, allowing acquisition times of less than one second and images virtually free of motion-induced artifacts during quiet respiration. Fifteen patients with known liver lesions (metastases, hemangiomas, and cysts) were examined using T1- and T2-weighted 2-dimensional MP-RAGE sequences, and the images were compared with conventional T1- and multi-echo T2-weighted spin-echo (SE) sequences. Signal difference-to-noise ratios (SD/Ns) of the lesions were calculated for all pulse sequences using corresponding axial images and were normalized for voxel volume. The mean normalized SD/Ns of the MP-RAGE sequences were generally comparable to those for the SE sequences. In addition, there were no noticeable respiratory artifacts on the MP-RAGE images whereas these were clearly present on the T2-weighted SE images and to a lesser degree on the T1-weighted SE images. It is concluded that the MP-RAGE technique could become an important method for evaluating the liver for focal disease.

Cysts↗
PubMed2006

Evaluation of drainage patterns of the major anastomotic veins on the lateral surface of the cerebrum using three-dimensional contrast-enhanced MP-RAGE sequence.

BACKGROUND AND PURPOSE: Three-dimensional (3D) contrast-enhanced magnetization-prepared rapid gradient-echo (MP-RAGE) sequence has been reported useful for evaluation of the intracranial venous structures. The purpose of this study is to assess the patterns of the major anastomotic veins on the lateral surface of the cerebrum using MP-RAGE sequence. METHODS: MP-RAGE images in consecutive 100 patients (200 sides) were reviewed by two neuroradiologists in consensus to evaluate drainage patterns of the superficial middle cerebral vein (SMCV), the vein of Labbe, and the Trolard vein. RESULTS: MP-RAGE images clearly depicted the major anastomotic veins and their draining vessel. The dominant vein was the Trolard vein in 12%, the vein of Labbe in 36%, SMCV in 38%, and all three veins in 14%. The vein of Labbe was entered the transverse sinus in 80% and superior petrosal sinus in 4%. Undeveloped type of the vein of Labbe was seen in 16%. The SMCVs were entered the sphenoparietal sinus in 57%, the cavernous sinus in 19%, and the emissary vein in 5%. Basal type of the SMCVs was seen in 3% and undeveloped type in 16%. It was difficult to differentiate the Trolard vein from other cortical veins, if it was not dominant. In the most cases with the dominant Trolard vein, it located at the level of the post central vein. CONCLUSION: With MP-RAGE sequence, it is easy to identify the variation of the major anastomotic veins. Such information may be helpful to reduce the risk of damage on these important veins at surgery.

Adolescent↗
PubMed2006

In vitro inhibition of transthyretin aggregate-induced cytotoxicity by full and peptide derived forms of the soluble receptor for advanced glycation end products (RAGE).

Familial amyloidotic polyneuropathy is a neurodegenerative disorder characterized by systemic extracellular deposition of transthyretin (TTR) amyloid fibrils. The latter have been proposed to trigger neurodegeneration through engagement of the receptor for advanced glycation end products (RAGE). Here we show that TTR interaction with RAGE is conserved across mouse and human species and is not dependent on RAGE glycosylation. Moreover, strand D of TTR structure seems important for the TTR-RAGE interaction as well as a motif in RAGE (residues 102-118) located within the V-domain; this motif suppressed TTR aggregate-induced cytotoxicity in cell culture.

Animals↗
PubMed2004

Advanced glycation end products induce tubular epithelial-myofibroblast transition through the RAGE-ERK1/2 MAP kinase signaling pathway.

Advanced glycation end products (AGEs) have been shown to play a role in tubular epithelial-myofibroblast transdifferentiation (TEMT) in diabetic nephropathy, but the intracellular signaling pathway remains unknown. We report here that AGEs signal through the receptor for AGEs (RAGE) to induce TEMT, as determined by de novo expression of a mesenchymal marker (alpha-smooth muscle actin, alpha-SMA) and loss of epithelial marker (E-cadherin), directly through the MEK1-ERK1/2 MAP kinase pathway, which is TGF-beta independent. This is supported by the following findings: AGEs induced de novo alpha-SMA mRNA expression as early as 2 hours followed by a loss of E-cadherin before TGF-beta mRNA expression at 24 hours and occurred in the absence of TGF-beta and AGE-induced activation of ERK1/2 MAP kinase at 15 minutes and TEMT at 24 hours were completely blocked by a neutralizing RAGE antibody, a soluble RAGE receptor, an ERK1/2 MAP kinase inhibitor (PD98059), and DN-MEK1, but not by a neutralizing TGF-beta antibody. Thus, this study demonstrates that AGEs activate the RAGE-ERK1/2 MAP kinase pathway to mediate the early TEMT process. The findings from this study suggest that targeting the RAGE or the ERK MAP kinase pathway may provide new therapeutic strategies for diabetic nephropathy and shed new light on the pathogenesis of diabetic nephropathy.

Actins↗
PubMed2003

RAGE-mediated MAPK activation by food-derived AGE and non-AGE products.

Investigating the cellular effects of food compounds formed by heat treatment during processing, we recently demonstrated the expression of the receptor for advanced glycation endproducts (RAGE) and the p44/42 MAP kinase activation by casein-N(epsilon )-(carboxymethyl)lysine (casein-CML), a food-derived AGE, in the intestinal cell line Caco-2. In this work, we report a Caco-2 p44/42 MAP kinase activation by bread crust and coffee extract. After identification, quantification, and synthesis of two key compounds formed in association with the process-induced heat impact applied to bread dough and coffee beans, those compounds, namely the AGE pronyl-glycine and the non-AGE N-methylpyridinium, were also demonstrated for the first time to activate the p44/42 MAP kinase through binding to RAGE in Caco-2 cells. Blocking of RAGE by an antagonistic antibody and expression of C-terminally truncated RAGE resulted in a reduced Caco-2- and HEK-293-MAP kinase activation. These findings unequivocally point to a RAGE-mediated activating effect of chemically defined food-derived, thermally generated products, both, AGEs and non-AGEs, on cellular signal transduction pathways involved in inflammatory response and cellular proliferation.

Antibodies↗
PubMedDate not supplied

Skull base tumors: evaluation with contrast-enhanced MP-RAGE sequence.

The purpose of this study is to assess the value of contrast-enhanced MP-RAGE sequence for evaluation of skull base tumors. A total of 36 patients were prospectively evaluated. MP-RAGE showed relatively higher CNRs than other sequences, and there was a significant difference of CNR between the MP-RAGE and contrast T1-weighted SE images when fat tissue was chosen as the background. MP-RAGE was significantly superior to other sequences in the diagnosis of the extent of tumors. Contrast-enhanced MP-RAGE sequence is useful in evaluation of skull base tumors because of its higher contrast, higher spatial resolution, multiplanar capability, and suppression of the fat signal.

Adolescent↗
PubMed2005

Polymorphisms of the receptor of advanced glycation endproducts (RAGE) and the development of nephropathy in type 1 diabetic patients.

OBJECTIVES: We investigated the association of the RAGE (Receptor for Advanced Glycation End products) exon3 gene polymorphisms with stages of nephropathy in type 1 diabetes. METHODS: The RAGE exon 3 genotype was assessed by Denaturing Gradient Gel Electrophoresis (DGGE) procedure in 487 type 1 diabetic patients with proliferative retinopathy subdivided into four groups according to their level of renal involvement and in 351 control subjects (GENEDIAB study). RESULTS: We reported here three main low frequency dimorphisms, previously submitted to data banks, Gly82Ser, Val89 CTC/CTG, and Arg77Cys. The genotype distribution of these polymorphisms was not statistically different in type 1 diabetic patients compared to healthy controls (p=0.37). Among the three described polymorphisms, only the RAGE Gly82Ser genotype frequency was significantly increased in the group with advanced nephropathy (11%) defined by a chronic renal failure compared to the three others groups: no nephropathy, 5%; incipient (microalbuminuria) 5%; established (macroalbuminuria), 2%) (P=0.04). The 82 Ser allele was identified as an independent risk marker for the stage of advanced nephropathy: adjusted odds ratio 3.17(95% CI 1,32-7,85, p=0.008). CONCLUSION: These data suggest that the 82 Ser allele of the RAGE gene is a risk allele for developing advanced nephropathy. This suggests that some RAGE gene polymorphisms may be associated with progression to diabetic advanced nephropathy in Caucasian type 1 diabetic patients.

Amino Acid Substitution↗
PubMed1997

RAGE mRNA expression in the diabetic mouse kidney.

Receptors for advanced glycation end products (RAGE), which bind and internalize AGE-modified proteins formed from oxidation and other products of the nonenzymatic glycation reaction, have been mechanistically implicated in the development of the chronic complications of diabetes. In the present experiments, we sought evidence for the participation of RAGE in diabetic nephropathy by analysis of steady state levels of mRNA encoding RAGE in the renal cortex of a well-defined animal model (the db/db mouse) that develops renal pathology similar to that found in human diabetes. In these animals, increased AGE-product formation was confirmed by measurement of fluorescence in serum and renal cortex proteins. Renal involvement was confirmed by demonstration of increased urine albumin excretion and elevated serum creatinine concentrations relative to nondiabetic (db/m) littermate controls. Despite elevated concentrations of circulating and tissue AGE-modified proteins, the level of RAGE mRNA expression in renal cortex of diabetic mice did not significantly differ from that in nondiabetic littermate controls. The findings militate against changes in RAGE expression in the pathogenesis of renal abnormalities in this animal model.

Albuminuria↗
PubMed2003

Regulation of expression of sulfoglucuronyl carbohydrate (HNK-1), Amphoterin and RAGE in retinoic acid-differentiated P19 embryonal carcinoma cells.

HNK-1 antibody reactive sulfoglucuronyl carbohydrate (SGC) and SSEA-1 antibody reactive Lewis X (Lex) epitope are expressed on several glycolipids, glycoproteins, and proteoglycans of the nervous system and have been implicated in cell-cell recognition, neurite outgrowth, and/or neuronal migration during development. Interaction of SGC with its binding protein Amphoterin and interaction of Amphoterin with a cell-signaling molecule, receptor for advance glycation end product (RAGE) have been suggested to regulate neurite outgrowth and neuronal migration. The regulation of expression of SGC, Lex, Amphoterin, and RAGE was studied in embryonal carcinoma P19 cells after treatment with retinoic acid (RA). The untreated proliferating P19 cells strongly expressed the Lex epitope, which was mostly due to Lex-glycoproteins. P19 cells, when differentiated into neuron-like cells by RA, did not express the Lex epitope, but expressed increasing levels of SGC, with time in culture. Quantitative biochemical analyses showed that in the P19 cells after RA treatment, the amount of SGC-glycoproteins increased at a significantly higher level than sulfoglucuronyl glycolipid-1 (SGGL-1). The increase in the levels of SGGL-1 was due to 16-fold upregulation in the activity of lactosylceramide: N-acetylglucosaminyl-transferase (Lc3 synthase), which synthesizes the key intermediate lactotriosylceramide (Lc3Cer), for lacto- and neolacto-glycolipids. The large increase in the activity of Lc3 synthase appeared to regulate the levels of other neolacto glycolipids, such as Lc3Cer, nLc4Cer, nLc6Cer, disialosyl-nLc4Cer (LD1), and Lex-glycolipids. Strong upregulation of glucuronyl-transferase and modest twofold enhancement in the activity of the glucuronyl-sulfotransferase, which catalyze the final steps in the SGC synthesis, also would account for the large increase in the synthesis SGC-glycoproteins. RA also upregulated the synthesis of Amphoterin and RAGE in P19 cells. SGC, RAGE, and Amphoterin were co-localized in the RA-differentiated neurons. The initiation of neurite outgrowth along with co-ordinated upregulation of Amphoterin, RAGE, SGC-glycoproteins, and SGGLs in RA-treated P19 cells support the hypothesis that these molecules are involved in the neuronal process formation.

Animals↗
PubMed2000

RAGE: a multiligand receptor contributing to the cellular response in diabetic vasculopathy and inflammation.

RAGE is a multiligand member of the immunoglobulin superfamily of cell surface molecules whose properties extend the paradigm of ligand-receptor interactions. The receptor recognizes families of ligands with diverse structural features, such as advanced glycation endproducts (AGEs), amyloidogenic peptides/polypeptides, amphoterins, and S100/calgranulins rather than individual species. Engagement of RAGE by its ligands upregulates the receptor and initiates a cycle of sustained cellular perturbation; increased levels of RAGE on the cell surface make it an ideal target for subsequent ligand interactions and for propagating cellular dysfunction. At this time, the only means known to break this apparently vicious cycle appears to be blocking access to RAGE or removing the ligands. Taken together, these data suggest that RAGE has the potential to function as a progression factor in a range of disorders (AGEs are relevant to diabetes and other settings of oxidant stress, amyloidogenic peptides are relevant to amyloidoses, S100/calgranulins are relevant to inflammatory disorders, etc.) in which its ligands accumulate. The chronic juxtaposition of ligand and receptor triggers sustained cellular perturbation favoring mechanisms eventuating in tissue injury rather than those that would restore homeostasis.

Animals↗
PubMed2003

S100B inhibits myogenic differentiation and myotube formation in a RAGE-independent manner.

S100B is a Ca(2+)-modulated protein of the EF-hand type with both intracellular and extracellular roles. S100B, which is most abundant in the brain, has been shown to exert trophic and toxic effects on neurons depending on the concentration attained in the extracellular space. S100B is also found in normal serum, and its serum concentration increases in several nervous and nonnervous pathological conditions, suggesting that S100B-expressing cells outside the brain might release the protein and S100B might exert effects on nonnervous cells. We show here that at picomolar to nanomolar levels, S100B inhibits myogenic differentiation of rat L6 myoblasts via inactivation of p38 kinase with resulting decrease in the expression of the myogenic differentiation markers, myogenin, muscle creatine kinase, and myosin heavy chain, and reduction of myotube formation. Although myoblasts express the multiligand receptor RAGE, which has been shown to transduce S100B effects on neurons, S100B produces identical effects on myoblasts overexpressing either full-length RAGE or RAGE lacking the transducing domain. This suggests that S100B affects myoblasts by interacting with another receptor and that RAGE is not the only receptor for S100B. Our data suggest that S100B might participate in the regulation of muscle development and regeneration by inhibiting crucial steps of the myogenic program in a RAGE-independent manner.

Animals↗
PubMed2004

RAGE axis: Animal models and novel insights into the vascular complications of diabetes.

Receptor for AGE (RAGE) is a multi-ligand member of the immunoglobulin superfamily of cell surface molecules. Engagement of RAGE by its signal transduction ligands evokes inflammatory cell infiltration and activation in the vessel wall. In diabetes, when fueled by oxidant stress, hyperglycemia, and superimposed stresses such as hyperlipidemia or acute balloon/endothelial denuding arterial injury, the ligand-RAGE axis amplifies vascular stress and accelerates atherosclerosis and neointimal expansion. In this brief synopsis, we review the use of rodent models to test these concepts. Taken together, our findings support the premise that RAGE is an amplification step in vascular inflammation and acceleration of atherosclerosis. Future studies must rigorously test the potential impact of RAGE blockade in human subjects; such trials are on the horizon.

Animals↗